Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts...Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.展开更多
BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-rel...BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.展开更多
Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organizati...Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organization of actin cytoskeleton,we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and sizes.It was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern,but were absent from the opening edge of V-shaped pattern,indicating that the organization of actin cytoskeleton was dependent on the mechanical environment.Furthermore,a secondary actin ring was observed on 50μm circular pattern while did not appear on 30μm and 40μm pattern,showing a size-dependent organization of actin cytoskeleton.Finally,osteoblasts,MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern,suggesting a cell-type specificity in arrangement of actin cytoskeleton.Together,our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.展开更多
AIM:To investigate the effects of dexamethasone(DEX) and 1-(5-isoquinolinesulfonyl)-homopiperazine(HA1077) on actin cytoskeleton and β-catenin in cultured human trabecular meshwork(HTM) cells.METHODS: The H...AIM:To investigate the effects of dexamethasone(DEX) and 1-(5-isoquinolinesulfonyl)-homopiperazine(HA1077) on actin cytoskeleton and β-catenin in cultured human trabecular meshwork(HTM) cells.METHODS: The HTM cells were separated from human eyeball and cultured in vitro.They were divided into control group,DEX(1×10^-6mol/L) group,HA1077(3×10^-5mol/L)group,and DEX(1×10^-6mol/L) and HA1077(3×10^-5mol/L)group.Actin cytoskeleton and β-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot analyses.RESULTS: In DEX group,there were reorganization of actin cytoskeleton and formation of cross linked actin networks(CLANs),which were partially reversed in DEX and HA1077 group.DEX treatment also induced an increased expression of β-catenin,which was obviously reduced in DEX and HA1077 group.Meanwhile,the cultured HTM cells in HA1077 group had lower expression of β-catenin than that in the control group. CONCLUSION: Our results show that HA1077 can reverse the changes of actin organization and expression of β-catenin induced by DEX in cultured HTM cells,suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.展开更多
Pollen grains of Pinus thunbergii Parl. (Japanese black pine) were implanted with 30 keV nitrogen ion beams and the effects of nitrogen ion implantation on pollen tube growth in vitro and the organization of actin c...Pollen grains of Pinus thunbergii Parl. (Japanese black pine) were implanted with 30 keV nitrogen ion beams and the effects of nitrogen ion implantation on pollen tube growth in vitro and the organization of actin cytoskeleton in the pollen tube cell were investigated using a confocal laser scanning microscope after fluorescence labeling. Treatment with ion implantation significantly blocked pollen tube growth. Confocal microscopy showed that ion implantation disrupted actin filament cytoskeleton organization in the pollen tube. It was found that there was a distinct correlation between the inhibition of pollen tube growth and the disruption of actin cytoskeleton organization, indicating that an intact actin cytoskeleton is essential for continuous pollen tube elongation in Pinus thunbergii. Although the detailed mechanism for the ion-implantation-induced bioeffect still remains to be elucidated, the present study assumes that the cytoskeleton system in pollen grains may provide a key target in response to ion beam implantation and is involved in mediating certain subsequent cytological changes.展开更多
Objective:To examine the role of heat shock protein 90(Hsp90) in the maintenance of actin cytoskeleton in human neuroblastoma tumor cells.Methods:Co-precipitation experiments were performed to examine Hsp90 interactio...Objective:To examine the role of heat shock protein 90(Hsp90) in the maintenance of actin cytoskeleton in human neuroblastoma tumor cells.Methods:Co-precipitation experiments were performed to examine Hsp90 interaction with actin.Hsp90 and actin interactions were evaluated by protein refolding and acto-myosin motility assays.17-(AUylamino)-17- demethoxygeldanamycin(17AAG) induced actin-cytoskeleton re-organization was examined by laser scanning confocal microcopy.Results:It was shown that inhibition of Hsp90 by 17AAC accelerates detergent induced cell lysis of neuroblastoma tumor cells through destabilization of actin cytoskeleton.The in vitro co-precipitation experiments showed that functional but not mutant Hsp90 binds with F-actin.Among biochemical modifications,phopshorylation and oligomerization enhanced Hsp90 binding with F-actin.F-actin binding to Hsp90 interfered with Hsp90 chaperone activity in protein refolding assays,and Hsp90 binding to F-actin interfered with actin motility on myosin coated flow cell.In the combination treatment,17AAG irreversibly augmented the effect of cytochalasin D,an inhibitor of actin polymerization.Conclusions:It can be concluded that Hsp90 binds to F-actin in tumor cells and maintains the cellular integrity. The results display a novel element of Hsp90 inhibition in destabilizing the actin cytoskeleton of tumor cells,therefore suggest that 17AAG combination with cytoskeletal disruptor may be effective in combating cancer.展开更多
The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In rec...The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.展开更多
Hippo signaling plays a crucial role in growth control and tumor suppression by regulating cell proliferation,apoptosis,and differentiation.How Hippo signaling is regulated has been under extensive investigation.Over ...Hippo signaling plays a crucial role in growth control and tumor suppression by regulating cell proliferation,apoptosis,and differentiation.How Hippo signaling is regulated has been under extensive investigation.Over the past three years,an increasing amount of data have supported a model of actin cytoskeleton blocking Hippo signaling activity to allow nuclear accumulation of a downstream effector,Yki/Yap/Taz.On the other hand,Hippo signaling negatively regulates actin cytoskeleton organization.This review p rovides insight on the mutual regulatory mechanisms between Hippo signaling and actin cytoskeleton for a tight control of cell behaviors during animal development,and points out outstanding questions for further investigations.展开更多
The B cell antigen receptor (BCR) is the sensor on the B cell surface that surveys foreign molecules (antigen) in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. ...The B cell antigen receptor (BCR) is the sensor on the B cell surface that surveys foreign molecules (antigen) in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. The binding of antigen to the BCR induces signaling cascades in the cytoplasm, which provides the first signal for B cell activation. Subsequently, BCRs internalize and target bound antigen to endosomes, where antigen is processed into T cell recognizable forms. T helper cells generate the second activation signal upon binding to antigen presented by B cells. The optimal activation of B cells requires both signals, thereby depending on the coordination of BCR signaling and antigen transport functions. Antigen binding to the BCR also induces rapid remodeling of the cortical actin network of B cells. While being initiated and controlled by BCR signaling, recent studies reveal that this actin remodeling is critical for both the signaling and antigen processing functions of the BCR, indicating a role for actin in coordinating these two pathways. Here we will review previous and recent studies on actin reorganization during BCR activation and BCR- mediated antigen processing, and discuss how actin remodeling translates BCR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling.展开更多
Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not we...Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not well understood how these actin binding proteins are modulated in a physiological condition by their interaction proteins. In this study, we describe that Arabidopsis 14-3-3 λ protein interacted with actin depolymerizing factor 1(ADF1) in plant to regulate F-actin stability and dynamics. Loss of 14-3-3 λin Arabidopsis resulted in longer etiolated hypocotyls in dark and changed actin cytoskeleton architecture in hypocotyl cells. Overexpression of ADF1 repressed 14-3-3 λ mutant hypocotyl elongation and actin dynamic phenotype. In addition, the phosphorylation level of ADF1 was increased and the subcellular localization of ADF1 was altered in 14-3-3 λ mutant. Consistent with these observations, the actin filaments were more stable in 14-3-3 λ mutant. Our results indicate that 14-3-3 λ protein mediates F-actin dynamics possibly through inhibiting ADF1 phosphorylation in vivo.展开更多
The actin cytoskeleton is an important component of eukaryotic cell cytoskeleton and is temporally and spatially controlled by a series of actin binding proteins (ABPs). Among ABPs, formin family proteins have attract...The actin cytoskeleton is an important component of eukaryotic cell cytoskeleton and is temporally and spatially controlled by a series of actin binding proteins (ABPs). Among ABPs, formin family proteins have attracted much attention as they can nucleate unbranched actin filament from the profilin bound actin pool in vivo. In recent years, a number of formin family members from different organisms have been reported, and their characteristics are known more clearly, although some questions are still to be clarified. Here, we summarize the structures, func-tions and nucleation mechanisms of different formin family proteins, intending to compare them and give some new clues to the study of formins.展开更多
The formation of the polarity of pollen proto-plast and the dynamics of actin cytoskeleton were observed by non-fixation, Alexa-Phalloidin probing and confocal laser scanning microscopy. Our results showed that the pr...The formation of the polarity of pollen proto-plast and the dynamics of actin cytoskeleton were observed by non-fixation, Alexa-Phalloidin probing and confocal laser scanning microscopy. Our results showed that the protoplast obtained from stored pollen contained numerous crystalline fusiform bodies to constitute a storage form of actin. When dormant pollen was hydrated, the actin cytoskeleton forms a fine network spreading uniformly in the protoplast. In the process of polarity formation and germination of pollen pro-toplast, actin filaments marshaled slowly to the brim, and then formed multilayer continuous actin filament bundles surrounding the cortical of the protoplast. When the proto-plast was exposed to actin filament-disrupting drugs, such as Latrunculin A and Cytochalasin D, continuously arranged actin bundles were disturbed and in this condition, the pro-toplast could not germinate. But when exposed to actin fila-ment stabiling drug-phalliodin, the dynamics of actin fila-ments in the protoplasts behaved normally and the proto-plasts could germinate normally. These results were also confirmed by the pharmacology experiments on pollen grains. And when Latrunculin A or Cytochalasin D was washed off, the ratio of pollen germination was resumed partly. All the results above show that the dynamic organiza-tion of the actin cytoskeleton are critical in the cell polarity formation and germination of pollen protoplast, and that the reorganization of actin cytoskeleton is mainly due to the re-arrangement of actin filament arrays.展开更多
In eukaryotic cells, the course of the cell cycle depends on correct cytoskeleton arrangement. The cell cycle consists of several phases, and in each of them the cytoskeleton has a unique structure and set of characte...In eukaryotic cells, the course of the cell cycle depends on correct cytoskeleton arrangement. The cell cycle consists of several phases, and in each of them the cytoskeleton has a unique structure and set of characteristics. The dynamics of the cytoskeleton together with its binding proteins greatly contribute to progression of the cell cycle. Here, we mainly review recent research on the dynamic distribution of the actin cytoskeleton and actin-binding proteins, and the mechanisms by which they affect the progression of the plant cell cycle.展开更多
Previous studies show that actin-binding Rho activating protein (Abra) is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central ne...Previous studies show that actin-binding Rho activating protein (Abra) is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord, Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.展开更多
基金supported by the National Natural Science Foundation of China(82171506 and 31872778)Discipline Innovative Engineering Plan(111 Program)of China(B13036)+3 种基金Key Laboratory Grant from Hunan Province(2016TP1006)Department of Science and Technology of Hunan Province(2021DK2001,Innovative Team Program 2019RS1010)Innovation-Driven Team Project from Central South University(2020CX016)Hunan Hundred Talents Program for Young Outstanding Scientists。
文摘Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.
文摘BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.
基金This work was supported by the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030009)the National Key Research and Development Program of China(2022YFC3400600)National Natural Science Foundation of China(12174208,32227802,11874231,31801134 and 31870843)+2 种基金Tianjin Natural Science Foundation(20JCYBJC01010)China Postdoctoral Science Foundation(2020M680032)Fundamental Research Funds for the Central Universities(2122021337 and 2122021405).
文摘Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organization of actin cytoskeleton,we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and sizes.It was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern,but were absent from the opening edge of V-shaped pattern,indicating that the organization of actin cytoskeleton was dependent on the mechanical environment.Furthermore,a secondary actin ring was observed on 50μm circular pattern while did not appear on 30μm and 40μm pattern,showing a size-dependent organization of actin cytoskeleton.Finally,osteoblasts,MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern,suggesting a cell-type specificity in arrangement of actin cytoskeleton.Together,our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.
基金Supported by the Natural Science Foundation of China (No.81300768 No.81371048+4 种基金 No.81670853)Science and Technology Department of Sichuan Province of China (No.2015HH0031)Health and Family Planning Commission of Sichuan Province of China (No.100539 No. 090505 No.090514)
文摘AIM:To investigate the effects of dexamethasone(DEX) and 1-(5-isoquinolinesulfonyl)-homopiperazine(HA1077) on actin cytoskeleton and β-catenin in cultured human trabecular meshwork(HTM) cells.METHODS: The HTM cells were separated from human eyeball and cultured in vitro.They were divided into control group,DEX(1×10^-6mol/L) group,HA1077(3×10^-5mol/L)group,and DEX(1×10^-6mol/L) and HA1077(3×10^-5mol/L)group.Actin cytoskeleton and β-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot analyses.RESULTS: In DEX group,there were reorganization of actin cytoskeleton and formation of cross linked actin networks(CLANs),which were partially reversed in DEX and HA1077 group.DEX treatment also induced an increased expression of β-catenin,which was obviously reduced in DEX and HA1077 group.Meanwhile,the cultured HTM cells in HA1077 group had lower expression of β-catenin than that in the control group. CONCLUSION: Our results show that HA1077 can reverse the changes of actin organization and expression of β-catenin induced by DEX in cultured HTM cells,suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.
基金National Science Foundation of Fujian Province of China(No.B0610031)Science and Technology Program of Put-Jan Municipality of China(No.2006N17)
文摘Pollen grains of Pinus thunbergii Parl. (Japanese black pine) were implanted with 30 keV nitrogen ion beams and the effects of nitrogen ion implantation on pollen tube growth in vitro and the organization of actin cytoskeleton in the pollen tube cell were investigated using a confocal laser scanning microscope after fluorescence labeling. Treatment with ion implantation significantly blocked pollen tube growth. Confocal microscopy showed that ion implantation disrupted actin filament cytoskeleton organization in the pollen tube. It was found that there was a distinct correlation between the inhibition of pollen tube growth and the disruption of actin cytoskeleton organization, indicating that an intact actin cytoskeleton is essential for continuous pollen tube elongation in Pinus thunbergii. Although the detailed mechanism for the ion-implantation-induced bioeffect still remains to be elucidated, the present study assumes that the cytoskeleton system in pollen grains may provide a key target in response to ion beam implantation and is involved in mediating certain subsequent cytological changes.
基金supported by Department of Biotechnology,Department of Science and Technology,Government of India
文摘Objective:To examine the role of heat shock protein 90(Hsp90) in the maintenance of actin cytoskeleton in human neuroblastoma tumor cells.Methods:Co-precipitation experiments were performed to examine Hsp90 interaction with actin.Hsp90 and actin interactions were evaluated by protein refolding and acto-myosin motility assays.17-(AUylamino)-17- demethoxygeldanamycin(17AAG) induced actin-cytoskeleton re-organization was examined by laser scanning confocal microcopy.Results:It was shown that inhibition of Hsp90 by 17AAC accelerates detergent induced cell lysis of neuroblastoma tumor cells through destabilization of actin cytoskeleton.The in vitro co-precipitation experiments showed that functional but not mutant Hsp90 binds with F-actin.Among biochemical modifications,phopshorylation and oligomerization enhanced Hsp90 binding with F-actin.F-actin binding to Hsp90 interfered with Hsp90 chaperone activity in protein refolding assays,and Hsp90 binding to F-actin interfered with actin motility on myosin coated flow cell.In the combination treatment,17AAG irreversibly augmented the effect of cytochalasin D,an inhibitor of actin polymerization.Conclusions:It can be concluded that Hsp90 binds to F-actin in tumor cells and maintains the cellular integrity. The results display a novel element of Hsp90 inhibition in destabilizing the actin cytoskeleton of tumor cells,therefore suggest that 17AAG combination with cytoskeletal disruptor may be effective in combating cancer.
基金supported in part by a Barnett Rosenberg Fellowship in Biological Sciences from Michigan State Universitysupported by the National Science Foundation(IOS-1021044)
文摘The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.
基金This work was partly supported by the National Science Foundation.
文摘Hippo signaling plays a crucial role in growth control and tumor suppression by regulating cell proliferation,apoptosis,and differentiation.How Hippo signaling is regulated has been under extensive investigation.Over the past three years,an increasing amount of data have supported a model of actin cytoskeleton blocking Hippo signaling activity to allow nuclear accumulation of a downstream effector,Yki/Yap/Taz.On the other hand,Hippo signaling negatively regulates actin cytoskeleton organization.This review p rovides insight on the mutual regulatory mechanisms between Hippo signaling and actin cytoskeleton for a tight control of cell behaviors during animal development,and points out outstanding questions for further investigations.
文摘The B cell antigen receptor (BCR) is the sensor on the B cell surface that surveys foreign molecules (antigen) in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. The binding of antigen to the BCR induces signaling cascades in the cytoplasm, which provides the first signal for B cell activation. Subsequently, BCRs internalize and target bound antigen to endosomes, where antigen is processed into T cell recognizable forms. T helper cells generate the second activation signal upon binding to antigen presented by B cells. The optimal activation of B cells requires both signals, thereby depending on the coordination of BCR signaling and antigen transport functions. Antigen binding to the BCR also induces rapid remodeling of the cortical actin network of B cells. While being initiated and controlled by BCR signaling, recent studies reveal that this actin remodeling is critical for both the signaling and antigen processing functions of the BCR, indicating a role for actin in coordinating these two pathways. Here we will review previous and recent studies on actin reorganization during BCR activation and BCR- mediated antigen processing, and discuss how actin remodeling translates BCR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling.
基金supported by the National Basic Research Program of China(2012CB114200)Foundation for Innovative Research Group of the National Natural Science Foundation of China(31421062)
文摘Actin cytoskeleton dynamics is critical for variety of cellular events including cell elongation, division and morphogenesis, and is tightly regulated by numerous groups of actin binding proteins. However it is not well understood how these actin binding proteins are modulated in a physiological condition by their interaction proteins. In this study, we describe that Arabidopsis 14-3-3 λ protein interacted with actin depolymerizing factor 1(ADF1) in plant to regulate F-actin stability and dynamics. Loss of 14-3-3 λin Arabidopsis resulted in longer etiolated hypocotyls in dark and changed actin cytoskeleton architecture in hypocotyl cells. Overexpression of ADF1 repressed 14-3-3 λ mutant hypocotyl elongation and actin dynamic phenotype. In addition, the phosphorylation level of ADF1 was increased and the subcellular localization of ADF1 was altered in 14-3-3 λ mutant. Consistent with these observations, the actin filaments were more stable in 14-3-3 λ mutant. Our results indicate that 14-3-3 λ protein mediates F-actin dynamics possibly through inhibiting ADF1 phosphorylation in vivo.
基金This work was supported by the National Natural Science Foundation for Distinguished Young Scholars (Grant No. 30325005)the National Natural Science Foundation of China (Grant No. 30470176)the National Basic Research Program of China (Grant No. 2006CB 100100).
文摘The actin cytoskeleton is an important component of eukaryotic cell cytoskeleton and is temporally and spatially controlled by a series of actin binding proteins (ABPs). Among ABPs, formin family proteins have attracted much attention as they can nucleate unbranched actin filament from the profilin bound actin pool in vivo. In recent years, a number of formin family members from different organisms have been reported, and their characteristics are known more clearly, although some questions are still to be clarified. Here, we summarize the structures, func-tions and nucleation mechanisms of different formin family proteins, intending to compare them and give some new clues to the study of formins.
文摘The formation of the polarity of pollen proto-plast and the dynamics of actin cytoskeleton were observed by non-fixation, Alexa-Phalloidin probing and confocal laser scanning microscopy. Our results showed that the protoplast obtained from stored pollen contained numerous crystalline fusiform bodies to constitute a storage form of actin. When dormant pollen was hydrated, the actin cytoskeleton forms a fine network spreading uniformly in the protoplast. In the process of polarity formation and germination of pollen pro-toplast, actin filaments marshaled slowly to the brim, and then formed multilayer continuous actin filament bundles surrounding the cortical of the protoplast. When the proto-plast was exposed to actin filament-disrupting drugs, such as Latrunculin A and Cytochalasin D, continuously arranged actin bundles were disturbed and in this condition, the pro-toplast could not germinate. But when exposed to actin fila-ment stabiling drug-phalliodin, the dynamics of actin fila-ments in the protoplasts behaved normally and the proto-plasts could germinate normally. These results were also confirmed by the pharmacology experiments on pollen grains. And when Latrunculin A or Cytochalasin D was washed off, the ratio of pollen germination was resumed partly. All the results above show that the dynamic organiza-tion of the actin cytoskeleton are critical in the cell polarity formation and germination of pollen protoplast, and that the reorganization of actin cytoskeleton is mainly due to the re-arrangement of actin filament arrays.
基金supported by the National Natural Science Foundation of China (30870211, 30970174)the National Basic Research Program of China (2007CB108700)the Chinese Transgenic Project (2009ZX08009-059B) to H. Ren
文摘In eukaryotic cells, the course of the cell cycle depends on correct cytoskeleton arrangement. The cell cycle consists of several phases, and in each of them the cytoskeleton has a unique structure and set of characteristics. The dynamics of the cytoskeleton together with its binding proteins greatly contribute to progression of the cell cycle. Here, we mainly review recent research on the dynamic distribution of the actin cytoskeleton and actin-binding proteins, and the mechanisms by which they affect the progression of the plant cell cycle.
基金supported by the National Natural Science Foundation of China,No.30971532Ph.D.Programs Foundation of Ministry of Education of China,No.20090162110063+1 种基金the Natural Science Foundation of Hunan Province,No.09JJ5015the Scientific Research Program of Hunan Provincial Higher Education Institutes,No.110541
文摘Previous studies show that actin-binding Rho activating protein (Abra) is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord, Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.
文摘洋葱鳞茎内表皮细胞经Triton X-100处理和多聚甲醛固定之后用Rh-Ph(Rhodamine-Phalloidin)染色,细胞质内可见较丰富的、直径为100—300nm的F-actin束。较粗的F-actin束沿细胞的长轴平行排列,并纵裂成较细的“分枝”,纵裂成的分枝又纵裂成更细的“分枝”。各种大小的F-actin束相互交织在一起构成一个三维的纤丝网络,并且与细胞膜、细胞核和其它细胞器相连。经同样方法处理和固定的细胞用考马斯亮兰R_(250)(Coomassie brilliant blue R_(250))染色之后,细胞质内可见直径为200—300nm的纤丝,形态特征和排列方式和上述在荧光显微镜下看到的F-actin束相同。本研究结果表明洋葱鳞茎内表皮的细胞骨架包含较丰富的F-actin系统;Pena的考马斯亮兰染色法(1980)所显示的结构主要代表F-actin束。