Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerativ...Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.展开更多
BACKGROUND: It is suspected that dissociation, destruction or synthetic disorder of microtubule-associated protein 2 (MAP-2) may participate in secondary injury of intracerebral hemorrhage (ICH), and the reason m...BACKGROUND: It is suspected that dissociation, destruction or synthetic disorder of microtubule-associated protein 2 (MAP-2) may participate in secondary injury of intracerebral hemorrhage (ICH), and the reason may be related to thrombin in high concentration after ICH; therefore, the mechanism should be studied further. OBJECTIVE: To explore the effect of hirudin on expression of MAP-2 in peripheral tissue of hematom after ICH and changes of water content in brain tissue and analyze pathogenesis of thrombin in secondary injury after ICH. DESIGN : Completely randomized grouping design and controlled animal study SEn-ING : Department of Neurology, the First Affiliated Hospital of Jilin University MATERIALS : The experiment was carried out in the Neurological Laboratory of the First Affiliated Hospital of Jilin University from April 2003 to April 2004. A number of 80 healthy Wistar rats, of both genders, aged 3-4 months, weighing 250-350 g, were randomly divided into 8 groups: normal control group, 6-hour ICH group, 1-day ICH group, 2-day ICH group, 3-day ICH group, 7-day ICH group, 3-day hirudin group and 7-day hirudin group with 10 in each group. Five rats from each group were selected to measure their water content, and the others were undertaken immunohistochemical stain. Hirudin was produced by Sigma Company, USA, and MAP-2 rabbit-rat polyclonal antibody was provided by Fuzhou Maixin Biotechnology Company Limited. METHODS: ① Model establishing and grouping intervention: Rats in simple ICH group were collected their blood from tails and then inserted with 50 μL non-anticoagulant auto-arterial blood into the cauda of the putamen in right brain within 5 minutes. Rats in hirudin groups were inserted with 10 U hirudin (which was diluted with saline to 20 μL) into local hematom regions within 5 minutes, and the needle was pulled out after 10 minutes. Rats in normal control group were untouched. ② Water content in peripheral tissue of hematom: Based on the ratio between dry weight and wet weight, brain tissue at bleeding side and in right frontal lobe was selected to measure dry and wet weights so as to calculate the water content [(wet weight - dry weight) /wet weight] × 100%.③ Positive expression of MAP-2: Based on immunohistochemical stain, positive MAP-2 cells were regarded as neurons and they were buffy morphological. Positive rate of MAP-2 was calculated, i.e., percentage of positive cells in each sight to total cells in all sights. ④ Statistical analysis: Data among groups were compared with one-way analysis of variance, averages were compared with SNK-q test by each other, and relation between water content and MAP-2 was analyzed with linear regression technique. MAIN OUTCOME MEASURES: Changes of water content and MAP-2 expression in peripheral tissue of hematorn at various time points after ICH and intervention of hirudin. RESULTS: All 80 rats were involved in the final analysis. ①Water content: Water content was increased at day 1, reached peak at day 3 and decreased at day 7. It was (72.31±0.32)%, (77.42±0.53)%, (78.44±0.28)%, (74.10±0.13)%, (74.85±0.51)% and (70.07±0.36)%, respectively in 1-day, 2-day, 3-day and 7-day ICH groups and 3-day and 7-day hirudin groups, which was higher than that in normal control group (63.85±0.41, q=-4.684 3 to -7.262 0, P〈 0.05); that in 2-day and 3-day ICH groups was higher than that in 7-day ICH group (q=-3.053 4, -3.727 0, P 〈 0.05); and that in 3-day and 7-day ICH groups was higher than that in hirudin groups at the same time points (q=-2.965 6, -2.726 4, P 〈 0.05). ②Positive expression of MAP-2: Positive expression of MAP-2 was decreased at 6 hours after ICH, reached the lowest value at day 3 and increased at day 7. Positive rate was (78.60±0.42)%, (60.56±0.74)%, (44.60±0.26)%, (25.45±0.85)%, (32.55±0.64)%, (37.69+0.76)%, (41.75±0.68)%, respectively in 6-hour, 1-day, 2-day, 3-day and 7-day ICH groups and 3-day and 7-day hirudin groups, which was lower than that in normal control group [(96.50±0.33)%, q= -3.074 5 to -8.128 5, P 〈 0.05]. In addition, positive cells of MAP-2 disappeared plentifully at 3-7 days after ICH, stain of positive cells were light, and only stain of plasma was positive. That in 3-day and 7-day hirudin groups was higher than that in ICH groups at the same time points (q= -3.391 8, -2.967 9, P 〈 0.05). Moreover, positive cells of MAP-2 was formed slightly but deeply stained. ③ Results of linear regression: Water content was negatively related to MAP-2 changes at 7 days after ICH (r= -0.894 9, P〈 0.01), i.e., water content was increased with decrease of MAP-2 expression. CONCLUSION : The deterioration of MAP-2 may be involved in the pathogenesis of thrombin within the first week after ICH, and the local administration of hirudin can protect neurons.展开更多
The present study was designed to determine microtubule-associated protein-2 and synaptophysin expression in the hippocampal CA3 region in a rat model of middle cerebral artery occlusion. The rats were treated with ac...The present study was designed to determine microtubule-associated protein-2 and synaptophysin expression in the hippocampal CA3 region in a rat model of middle cerebral artery occlusion. The rats were treated with acupuncture at Baihui (GV 20), Qubin (GB 7), and Qianding (GV 21) points, in addition to exercise training. Results were compared with rats undergoing exercise training only. The Y-maze method and immunohistochemistry revealed decreased error frequency of passing through Y-maze, as well as significantly increased microtubule-associated protein-2 and synaptophysin expression, in the acupuncture with exercise training group compared with the model and exercise training groups after 5 weeks. Microtubule-associated protein-2 and synaptophysin expressions negatively correlated with error frequency of passing through the Y-maze. These results suggested that acupuncture combined with exercise training improved learning and memory functions in a rat model of cerebral infarction. The mechanisms of action were hypothesized to be associated with dendritic or synaptic plasticity in the ipsilateral hippocampal CA3 region.展开更多
Following granulocyte colony-stimulating factor (G-CSF) treatment,the growth of processes in cul-tured rat retinal ganglion cells (RGCs) in vitro,expression of growth associated protein 43,and expression of microt...Following granulocyte colony-stimulating factor (G-CSF) treatment,the growth of processes in cul-tured rat retinal ganglion cells (RGCs) in vitro,expression of growth associated protein 43,and expression of microtubule-associated protein 2 mRNA expression were significantly increased.In contrast,RhoA/Rock protein content was significantly reduced by G-CSF treatment.These results indicate that G-CSF promotes the growth of processes in RGCs and increases the expression of growth-associated protein 43 and microtubule-associated protein 2 mRNA by inhibiting the RhoA/Rock pathway,thereby benefiting axonal repair in RGCs exposed to hypoxia.展开更多
Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young gro...Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young group (6 months) and an aged group (28 months) of 10 animals each. The two-step immunohistochemistry method with the antibody against tau protein and MAPa was performed with the testis tissues. Results: The immunoreactive cells of the testicular interstilial tau protein were significantly increased (P<0.01) and those of the MAP significantly decreased (P<0.01) in the aged than in the young rats. Conclusion: The changes in the expression of the tau protein and MAP may be related to the aging process of the testis.展开更多
In this review, we discuss the role of microtubule-associated protein 1 B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during...In this review, we discuss the role of microtubule-associated protein 1 B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAPIB in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.展开更多
An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the U...An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the UL25 protein demonstrated its co-localization with cellular microtubule-associated protein in the plasma membrane. Further investigations with deletion mutants suggest that UL25 is likely to have a function in the nucleus.展开更多
BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely ...BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.展开更多
As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphoryla...As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β(GSK-3β) and protein phosphatase 2A(PP2A) are the most implicated. Accumulation of the hyperphosphorylated tau induces synaptic toxicity and cognitive impairments. Here, we review the upstream factors or pathways that can regulate GSK-3β or PP2A activity mainly based on our recent findings. We will also discuss the mechanisms that may underlie tau-induced synaptic toxicity.展开更多
Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau express...Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration.展开更多
Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial...Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form.展开更多
Background Parvalbumin (PV), as a mobile endogenous calcium buffer, plays an important role in affecting temporospatial characteristics of calcium transients and in modulating calcium homeostasis. PV is expressed in...Background Parvalbumin (PV), as a mobile endogenous calcium buffer, plays an important role in affecting temporospatial characteristics of calcium transients and in modulating calcium homeostasis. PV is expressed in neurons in the dorsal root ganglion (DRG) and spinal dorsal horn and may be involved in synaptic transmission through regulating cytoplasm calcium concentrations. But the exact role of PV in peripheral sensory neurons remains unknown.Microtubule-associated protein 2 (MAP-2), belonging to structural microtubule-associated protein family, is especially vulnerable to acute central nervous system (CNS) injury, and there will be rapid loss of MAP-2 at the injury site. The present study investigated the changes of PV expressing neurons and the MAP-2 neurons in the DRG after an operation for chronic constriction injury to the unilateral sciatic nerve (CCI-SN), in order to demonstrate the possible roles of PV and MAP-2 in transmission and modulation of peripheral nociceptive information.Methods Seventy-two adult male Sprague-Dawley (SD) rats, weighing 180-220 g, were randomly divided into two groups (36 rats in each group), the sham operation group and chronic constriction injury (CCI) group. Six rats in each group were randomly selected to receive mechanical and thermal sensitivity tests at one day before operation and 1,3, 5,7, and 14 days after surgery. After pain behavioral test, ipsilateral lumbar fifth DRGs were removed and double immunofluorescence staining was performed to assess the expression changes of PV and of MAP2 expressing neurons in the L5 DRG before or after surgery.Results The animals with CCI-SN showed obvious mechanical allodynia and thermal hyperalgesia (P<0.05). Both the thermal and mechanical hyperalgesia decreased to their lowest degree at 7 days after surgery compared to the baseline before surgery (P<0.01). In normal rats before surgery, a large number of neurons were MAP-2 single labeled cells, and just a small number of PV-expressed neurons were found. PV-positive neurons, PV-positive nerve fibers and PV-negative neurons, formed a direct or close contact for cross-talk. We used immunocytochemical staining to quantify the time course of changes to PV and MAP-2 expressing neurons in tissue, and found that the number of PV expressing neurons began to slightly decrease at 3 days after surgery, and had a significant reduction at CCI day 5, day 7 (P<0.05). But MAP-2 neurons significantly decreased on just the 3rd day after CCI (P<0.05). No changes in PV and MAP-2 expression were almost found in sham operated rats. The number of PV positive neurons, was positively correlated with the hyperalgesia threshold.Conclusions A sharp decline in MAP-2 neurons may be the early response to surgical injury, and PV positive neurons were much more effective at affecting the changes of pain behaviors, indicating that the down-regulation of PV protein could participate in, at least in part, the modulation of nociceptive transmission.展开更多
Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral ...Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral transport is unclear.Hence,we aimed to explore how HBV manipulates microtubule-associated protein 1S(MAP1S)and microtubule(MT)to facilitate its transport and release.Methods:The expression of MAP1S or acetylated MT was investigated by immunofluorescence,RT-PCR,immunoblotting,and plasmid transfection.MAP1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection,respectively.HBV DNA was quantified using q-PCR.Results:Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR(p<0.01)and immunoblotting(p<0.001).Notably,stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls.MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells.Further,transfection with the hepatitis B virus X protein(HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls(p<0.0001),whereas HBVX−mutant-encoding HBV proteins(surface antigen,core protein,and viral DNA polymerase)hardly affected its expression.Conclusions:These results demonstrate that HBx induces the forma tion of stable MTs to promote the release of HBV particles through upregulating MAP1S.Thus,our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation,and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.展开更多
We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation....We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II (CKII) downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F-actin. Further investigation using extract of potato pollen indicated that a CKIl-like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKIl-like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.展开更多
In eukaryote cells,cargos are often transported cooperatively by kinesin motors and nonmotor microtubule-associated proteins(MAPs).The prior in vitro experimental data showed that the velocity of the cargo transported...In eukaryote cells,cargos are often transported cooperatively by kinesin motors and nonmotor microtubule-associated proteins(MAPs).The prior in vitro experimental data showed that the velocity of the cargo transported by kinesin motors and Ndc80(a member of MAP)proteins of truncated coiled-coil stalks decreases sensitively with the increase of the ratio of Ndc80 to motor number.However,the underlying mechanism of Ndc80 affecting sensitively the cooperative cargo transport by kinesin motors is unclear.To understand the mechanism,here we study numerically the cooperative cargo transport by kinesin motors and Ndc80 proteins.Our results showed that for the case of the motors and Ndc80 proteins with truncated short stalks,as used in the experiments,the calculated results reproduce quantitatively the prior experimental data.The mechanism of the cargo velocity decreasing sensitively with the ratio of Ndc80 to motor number is revealed.By contrast,for the case of the motors and Ndc80 proteins with full-length long stalks,the velocity of the cargo decreases slowly with the increase in the ratio of Ndc80 to kinesin number.Our results thus give an explanation of why the kinesin motors working in the cell have long stalks.展开更多
Autism spectrum disorder(ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain ...Autism spectrum disorder(ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain development is crucial to behavior and cognition in adulthood. Abnormal brain development, such as synaptic and myelin dysfunction, is involved in the pathogenesis of ASD. Microtubules and microtubule-associated proteins(MAPs) are important in regulating the processes of brain development, including neuron production and synaptic formation, as well as myelination. Increasing evidence suggests that the level of MAPs are changed in autistic patients and mouse models of ASD. Here, we discuss the roles of MAPs.展开更多
In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer...In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.展开更多
Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate...Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis.We examined the role of two DELLA proteins,GmRGAa and GmRGAb,in soybean plant height control.Knockout of these proteins led to longer internodes and increased plant height,primarily by increasing cell elongation.GmRGAs functioned under different light conditions,including red,blue,and far-red light,to repress plant height.Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b.Consistent with this,GmCRY1b partially regulated plant height via GmRGAs.Additionally,DELLA proteins were found to stabilize the protein GmSTF1/2,a key positive regulator of photomorphogenesis.This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height.This study enhances our understanding of DELLA-mediated plant height control,offering Gmrgaab mutants for soybean structure and yield optimization.展开更多
The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t...The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).展开更多
Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed th...Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.展开更多
基金supported by the National Natural Science Foundation of China,No.81130080,31300942the National Key Basic Research Program of China(973 Program)+5 种基金No.2014CB542202the Natural Science Foundation of Jiangsu Province,China,No.BK20150409the Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.15KJB180013the Scientific Research Foundation of Nantong University of China,No.14R29the Natural Science Foundation of Nantong City in China,No.MS12015043the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.
基金the Clinical KeyFoundation of Public HealthMinistry, No. 20013144
文摘BACKGROUND: It is suspected that dissociation, destruction or synthetic disorder of microtubule-associated protein 2 (MAP-2) may participate in secondary injury of intracerebral hemorrhage (ICH), and the reason may be related to thrombin in high concentration after ICH; therefore, the mechanism should be studied further. OBJECTIVE: To explore the effect of hirudin on expression of MAP-2 in peripheral tissue of hematom after ICH and changes of water content in brain tissue and analyze pathogenesis of thrombin in secondary injury after ICH. DESIGN : Completely randomized grouping design and controlled animal study SEn-ING : Department of Neurology, the First Affiliated Hospital of Jilin University MATERIALS : The experiment was carried out in the Neurological Laboratory of the First Affiliated Hospital of Jilin University from April 2003 to April 2004. A number of 80 healthy Wistar rats, of both genders, aged 3-4 months, weighing 250-350 g, were randomly divided into 8 groups: normal control group, 6-hour ICH group, 1-day ICH group, 2-day ICH group, 3-day ICH group, 7-day ICH group, 3-day hirudin group and 7-day hirudin group with 10 in each group. Five rats from each group were selected to measure their water content, and the others were undertaken immunohistochemical stain. Hirudin was produced by Sigma Company, USA, and MAP-2 rabbit-rat polyclonal antibody was provided by Fuzhou Maixin Biotechnology Company Limited. METHODS: ① Model establishing and grouping intervention: Rats in simple ICH group were collected their blood from tails and then inserted with 50 μL non-anticoagulant auto-arterial blood into the cauda of the putamen in right brain within 5 minutes. Rats in hirudin groups were inserted with 10 U hirudin (which was diluted with saline to 20 μL) into local hematom regions within 5 minutes, and the needle was pulled out after 10 minutes. Rats in normal control group were untouched. ② Water content in peripheral tissue of hematom: Based on the ratio between dry weight and wet weight, brain tissue at bleeding side and in right frontal lobe was selected to measure dry and wet weights so as to calculate the water content [(wet weight - dry weight) /wet weight] × 100%.③ Positive expression of MAP-2: Based on immunohistochemical stain, positive MAP-2 cells were regarded as neurons and they were buffy morphological. Positive rate of MAP-2 was calculated, i.e., percentage of positive cells in each sight to total cells in all sights. ④ Statistical analysis: Data among groups were compared with one-way analysis of variance, averages were compared with SNK-q test by each other, and relation between water content and MAP-2 was analyzed with linear regression technique. MAIN OUTCOME MEASURES: Changes of water content and MAP-2 expression in peripheral tissue of hematorn at various time points after ICH and intervention of hirudin. RESULTS: All 80 rats were involved in the final analysis. ①Water content: Water content was increased at day 1, reached peak at day 3 and decreased at day 7. It was (72.31±0.32)%, (77.42±0.53)%, (78.44±0.28)%, (74.10±0.13)%, (74.85±0.51)% and (70.07±0.36)%, respectively in 1-day, 2-day, 3-day and 7-day ICH groups and 3-day and 7-day hirudin groups, which was higher than that in normal control group (63.85±0.41, q=-4.684 3 to -7.262 0, P〈 0.05); that in 2-day and 3-day ICH groups was higher than that in 7-day ICH group (q=-3.053 4, -3.727 0, P 〈 0.05); and that in 3-day and 7-day ICH groups was higher than that in hirudin groups at the same time points (q=-2.965 6, -2.726 4, P 〈 0.05). ②Positive expression of MAP-2: Positive expression of MAP-2 was decreased at 6 hours after ICH, reached the lowest value at day 3 and increased at day 7. Positive rate was (78.60±0.42)%, (60.56±0.74)%, (44.60±0.26)%, (25.45±0.85)%, (32.55±0.64)%, (37.69+0.76)%, (41.75±0.68)%, respectively in 6-hour, 1-day, 2-day, 3-day and 7-day ICH groups and 3-day and 7-day hirudin groups, which was lower than that in normal control group [(96.50±0.33)%, q= -3.074 5 to -8.128 5, P 〈 0.05]. In addition, positive cells of MAP-2 disappeared plentifully at 3-7 days after ICH, stain of positive cells were light, and only stain of plasma was positive. That in 3-day and 7-day hirudin groups was higher than that in ICH groups at the same time points (q= -3.391 8, -2.967 9, P 〈 0.05). Moreover, positive cells of MAP-2 was formed slightly but deeply stained. ③ Results of linear regression: Water content was negatively related to MAP-2 changes at 7 days after ICH (r= -0.894 9, P〈 0.01), i.e., water content was increased with decrease of MAP-2 expression. CONCLUSION : The deterioration of MAP-2 may be involved in the pathogenesis of thrombin within the first week after ICH, and the local administration of hirudin can protect neurons.
文摘The present study was designed to determine microtubule-associated protein-2 and synaptophysin expression in the hippocampal CA3 region in a rat model of middle cerebral artery occlusion. The rats were treated with acupuncture at Baihui (GV 20), Qubin (GB 7), and Qianding (GV 21) points, in addition to exercise training. Results were compared with rats undergoing exercise training only. The Y-maze method and immunohistochemistry revealed decreased error frequency of passing through Y-maze, as well as significantly increased microtubule-associated protein-2 and synaptophysin expression, in the acupuncture with exercise training group compared with the model and exercise training groups after 5 weeks. Microtubule-associated protein-2 and synaptophysin expressions negatively correlated with error frequency of passing through the Y-maze. These results suggested that acupuncture combined with exercise training improved learning and memory functions in a rat model of cerebral infarction. The mechanisms of action were hypothesized to be associated with dendritic or synaptic plasticity in the ipsilateral hippocampal CA3 region.
文摘Following granulocyte colony-stimulating factor (G-CSF) treatment,the growth of processes in cul-tured rat retinal ganglion cells (RGCs) in vitro,expression of growth associated protein 43,and expression of microtubule-associated protein 2 mRNA expression were significantly increased.In contrast,RhoA/Rock protein content was significantly reduced by G-CSF treatment.These results indicate that G-CSF promotes the growth of processes in RGCs and increases the expression of growth-associated protein 43 and microtubule-associated protein 2 mRNA by inhibiting the RhoA/Rock pathway,thereby benefiting axonal repair in RGCs exposed to hypoxia.
文摘Objective: To examine the expression of the tau protein and mi-crotubule-associated proteins (MAP) in the testicular interstitium of aged and young rats. Methods: Sprague-Dawley male rats were divided into a young group (6 months) and an aged group (28 months) of 10 animals each. The two-step immunohistochemistry method with the antibody against tau protein and MAPa was performed with the testis tissues. Results: The immunoreactive cells of the testicular interstilial tau protein were significantly increased (P<0.01) and those of the MAP significantly decreased (P<0.01) in the aged than in the young rats. Conclusion: The changes in the expression of the tau protein and MAP may be related to the aging process of the testis.
基金supported by the National Natural Science Foundation of China(Establishment of corticospinal tract ischemic injury model in goat and axonal guidance of microtubule-associated protein 1B in bone marrow-derived mesenchymal stem cells migration in the spinal cord),No. 30972153
文摘In this review, we discuss the role of microtubule-associated protein 1 B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAPIB in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.
基金National Natural Science Funds(30570081, 30670094 and 30700028)
文摘An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the UL25 protein demonstrated its co-localization with cellular microtubule-associated protein in the plasma membrane. Further investigations with deletion mutants suggest that UL25 is likely to have a function in the nucleus.
基金Supported by the National Natural Science Foundation of China,No.U1504815 and No.U1504808
文摘BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.
文摘As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β(GSK-3β) and protein phosphatase 2A(PP2A) are the most implicated. Accumulation of the hyperphosphorylated tau induces synaptic toxicity and cognitive impairments. Here, we review the upstream factors or pathways that can regulate GSK-3β or PP2A activity mainly based on our recent findings. We will also discuss the mechanisms that may underlie tau-induced synaptic toxicity.
基金supported by the National Natural Science Foundation of China,No.81250016,31572217
文摘Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration.
基金supported by the Estate of Dr.Clem Jones AO and the Aus-tralia-China Joint Laboratory of Neuroscience and Cognition,as well as grants from the Australian Research Councilthe National Health and Medical Research Council of Australia to Jürgen Gtz
文摘Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form.
基金CAO Ming-hui and JI Feng-tao contributed equally to this study. This study was supported by a grant from the Natural Science Foundation of Guangdong Province (No. 7001595 ).
文摘Background Parvalbumin (PV), as a mobile endogenous calcium buffer, plays an important role in affecting temporospatial characteristics of calcium transients and in modulating calcium homeostasis. PV is expressed in neurons in the dorsal root ganglion (DRG) and spinal dorsal horn and may be involved in synaptic transmission through regulating cytoplasm calcium concentrations. But the exact role of PV in peripheral sensory neurons remains unknown.Microtubule-associated protein 2 (MAP-2), belonging to structural microtubule-associated protein family, is especially vulnerable to acute central nervous system (CNS) injury, and there will be rapid loss of MAP-2 at the injury site. The present study investigated the changes of PV expressing neurons and the MAP-2 neurons in the DRG after an operation for chronic constriction injury to the unilateral sciatic nerve (CCI-SN), in order to demonstrate the possible roles of PV and MAP-2 in transmission and modulation of peripheral nociceptive information.Methods Seventy-two adult male Sprague-Dawley (SD) rats, weighing 180-220 g, were randomly divided into two groups (36 rats in each group), the sham operation group and chronic constriction injury (CCI) group. Six rats in each group were randomly selected to receive mechanical and thermal sensitivity tests at one day before operation and 1,3, 5,7, and 14 days after surgery. After pain behavioral test, ipsilateral lumbar fifth DRGs were removed and double immunofluorescence staining was performed to assess the expression changes of PV and of MAP2 expressing neurons in the L5 DRG before or after surgery.Results The animals with CCI-SN showed obvious mechanical allodynia and thermal hyperalgesia (P<0.05). Both the thermal and mechanical hyperalgesia decreased to their lowest degree at 7 days after surgery compared to the baseline before surgery (P<0.01). In normal rats before surgery, a large number of neurons were MAP-2 single labeled cells, and just a small number of PV-expressed neurons were found. PV-positive neurons, PV-positive nerve fibers and PV-negative neurons, formed a direct or close contact for cross-talk. We used immunocytochemical staining to quantify the time course of changes to PV and MAP-2 expressing neurons in tissue, and found that the number of PV expressing neurons began to slightly decrease at 3 days after surgery, and had a significant reduction at CCI day 5, day 7 (P<0.05). But MAP-2 neurons significantly decreased on just the 3rd day after CCI (P<0.05). No changes in PV and MAP-2 expression were almost found in sham operated rats. The number of PV positive neurons, was positively correlated with the hyperalgesia threshold.Conclusions A sharp decline in MAP-2 neurons may be the early response to surgical injury, and PV positive neurons were much more effective at affecting the changes of pain behaviors, indicating that the down-regulation of PV protein could participate in, at least in part, the modulation of nociceptive transmission.
基金supported by the Research Fund of Beijing Institute of Hepatology(Y-2021-6)WBE Liver Fibrosis Foundation(WBE2021052)+1 种基金the Capital Special Fund for Health Development(2020-1-2182)the National Science and Technology Key Project of China(2017ZX10201201).
文摘Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral transport is unclear.Hence,we aimed to explore how HBV manipulates microtubule-associated protein 1S(MAP1S)and microtubule(MT)to facilitate its transport and release.Methods:The expression of MAP1S or acetylated MT was investigated by immunofluorescence,RT-PCR,immunoblotting,and plasmid transfection.MAP1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection,respectively.HBV DNA was quantified using q-PCR.Results:Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR(p<0.01)and immunoblotting(p<0.001).Notably,stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls.MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells.Further,transfection with the hepatitis B virus X protein(HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls(p<0.0001),whereas HBVX−mutant-encoding HBV proteins(surface antigen,core protein,and viral DNA polymerase)hardly affected its expression.Conclusions:These results demonstrate that HBx induces the forma tion of stable MTs to promote the release of HBV particles through upregulating MAP1S.Thus,our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation,and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.
基金Supported by the State Key Basic Research and Development Plan of China (2006CB100101)the National Natural Science Foundation of China (30421002, 30370707 and 30570925) to M.Yuan.
文摘We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II (CKII) downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F-actin. Further investigation using extract of potato pollen indicated that a CKIl-like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKIl-like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.
文摘In eukaryote cells,cargos are often transported cooperatively by kinesin motors and nonmotor microtubule-associated proteins(MAPs).The prior in vitro experimental data showed that the velocity of the cargo transported by kinesin motors and Ndc80(a member of MAP)proteins of truncated coiled-coil stalks decreases sensitively with the increase of the ratio of Ndc80 to motor number.However,the underlying mechanism of Ndc80 affecting sensitively the cooperative cargo transport by kinesin motors is unclear.To understand the mechanism,here we study numerically the cooperative cargo transport by kinesin motors and Ndc80 proteins.Our results showed that for the case of the motors and Ndc80 proteins with truncated short stalks,as used in the experiments,the calculated results reproduce quantitatively the prior experimental data.The mechanism of the cargo velocity decreasing sensitively with the ratio of Ndc80 to motor number is revealed.By contrast,for the case of the motors and Ndc80 proteins with full-length long stalks,the velocity of the cargo decreases slowly with the increase in the ratio of Ndc80 to kinesin number.Our results thus give an explanation of why the kinesin motors working in the cell have long stalks.
基金supported by National Natural Science Foundation of China (81671364 and 81201061)a China Postdoctoral Science Foundation Funded Project (2017M611195)the Outstanding Youth Talents Program of Shanxi Province, China (2015009)
文摘Autism spectrum disorder(ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain development is crucial to behavior and cognition in adulthood. Abnormal brain development, such as synaptic and myelin dysfunction, is involved in the pathogenesis of ASD. Microtubules and microtubule-associated proteins(MAPs) are important in regulating the processes of brain development, including neuron production and synaptic formation, as well as myelination. Increasing evidence suggests that the level of MAPs are changed in autistic patients and mouse models of ASD. Here, we discuss the roles of MAPs.
基金financially supported by the National Natural Science Foundation of China(U2004104)the Natural Science Foundation of Henan Province(202300410080)+2 种基金the Key Project of Henan Education Committee(21A310005)the Internal Fund of Hebei University of Economics and Business(2020ZD10)the Postgraduate“Talent Program”of Henan University(SYL20060187 and SYL20060189)。
文摘In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.
基金supported by the Sci-Tech Innovation 2030(2022ZD0400701-2)Agricultural Science and Technology Innovation Program of CAAS+1 种基金the National Natural Science Foundation of China(31871705)the Central Public-Interest Scientific Institution Basal Research Fund。
文摘Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis.We examined the role of two DELLA proteins,GmRGAa and GmRGAb,in soybean plant height control.Knockout of these proteins led to longer internodes and increased plant height,primarily by increasing cell elongation.GmRGAs functioned under different light conditions,including red,blue,and far-red light,to repress plant height.Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b.Consistent with this,GmCRY1b partially regulated plant height via GmRGAs.Additionally,DELLA proteins were found to stabilize the protein GmSTF1/2,a key positive regulator of photomorphogenesis.This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height.This study enhances our understanding of DELLA-mediated plant height control,offering Gmrgaab mutants for soybean structure and yield optimization.
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).
基金Indian Council of Medical Research,2020-0282/SCR/ADHOC-BMSDepartment of Science and Technology,India,DST/INSPIRE Fellowship:2021/IF210073.
文摘Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.