Damage to neurons in the central nervous system often leads to a permanent loss of function due to several factors,including reduced capacity of axons to regenerate and an environment that inhibits axon regeneration b...Damage to neurons in the central nervous system often leads to a permanent loss of function due to several factors,including reduced capacity of axons to regenerate and an environment that inhibits axon regeneration because of disruption of myelin and the formation of a growth-refractory glial scar around the injury（Yoon and Tuszynski,2012）.展开更多
With the support by the National Natural Science Foundation of China,a study by Prof.Zhu Yongqun’s(朱永群)research group from the Life Sciences Institute,Zhejiang University revealed that a conserved effector protein...With the support by the National Natural Science Foundation of China,a study by Prof.Zhu Yongqun’s(朱永群)research group from the Life Sciences Institute,Zhejiang University revealed that a conserved effector protein of bacterial MARTX toxins catalyzes N~ε-fatty acylation on the lysine residues in the C-展开更多
Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,an...Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.展开更多
BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules relate...BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules related to Rho GTPases. OBJECTIVE： To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases, including Rho-A, Rac-1, collapsin response mediator protein 1 （CRMP-1）, and tubulin 133 （Tub/33） during rat hippocampus development. DESIGN, TIME AND SETTING- A non-randomized, controlled, animal experiment, based on different developmental stages of the rat hippocampus, was performed at the Guangdong Key Laboratory of Tissue Construction and Detection, Institute of Clinical Anatomy, Southern Medical University between December 2005 and July 2007. MATERIALS： Trizol reagent was purchased from Invitrogen, USA. RNA PCR kit （AMV） Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa, Japan. Unless otherwise specified, all other reagents were purchased from Sigma-Aldrich, USA. METHODS： Twenty-five Sprague Dawley rats were assigned to five groups （n = 5） according to developmental stages： embryonic （embryonic 15 days）, neonatal （postnatal 5 days）, juvenile （postnatal 1 month）, adult （postnatal 3 months）, and senile （postnatal 18 months）. MAIN OUTCOME MEASURES： Detection of mRNA expression of Rho-A, Rac-1, CRMP-1, and Tub β3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction. RESULTS： Hippocampal mRNA expression of Rho-A, as well as Rac-1, reached peak levels at embryonic, juvenile, and senile stages, and was relatively less during neonatal and adult stages. mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage. CRMP-1 mRNA expression levels were as follows： embryonic 〉 neonatal 〉 juvenile 〉 adult 〈 senile, while Tubβ3 mRNA expression was embryonic 〉 neonatal 〉 juvenile 〉 adult = senile. CONCLUSION： Rho-A and Rac-1 shared similar expression profiles, which demonstrated similar variations during the entire rat hippocampus developmental process. However, Rac-1 mRNA expression remained greater than Rho-A. Both CRMP-1 and Tubβ3 mRNA expression profiles gradually declined during hippocampal development from embryonic to adult stages. Tubβ3 mRNA expression arrested during the adult stage, and CRMP-1 mRNA expression increased during the senile stage.展开更多
植物RHO相关蛋白GTPases(RHO-related GTPases of plants,ROPs)是广泛存在于植物中的一类信号转导G蛋白(又称GTP结合蛋白),其通过结合GDP或GTP在非活性和活性状态间进行切换,进而在细胞极性控制、形态发育、激素水平调控、逆境反应等诸...植物RHO相关蛋白GTPases(RHO-related GTPases of plants,ROPs)是广泛存在于植物中的一类信号转导G蛋白(又称GTP结合蛋白),其通过结合GDP或GTP在非活性和活性状态间进行切换,进而在细胞极性控制、形态发育、激素水平调控、逆境反应等诸多植物生命活动的信号转导过程中扮演重要的分子开关角色。本文对ROP蛋白的结构域及基于蛋白质结构分类进行了介绍,并对拟南芥、玉米、水稻和大麦中的ROP家族蛋白质进行了系统进化分析。分析结果表明,这些植物中的ROP蛋白根据蛋白质结构域组成可分为Ⅰ类(typeⅠ)和Ⅱ类(typeⅡ)两种类型,而根据蛋白质序列的保守性可将其在植物中的ROP蛋白划分为4个进化枝。本综述不但对ROP蛋白作为分子开关在细胞内调控各种信号通路的机制进行了叙述,还对ROP在花粉管、根毛及植物表皮铺盖细胞极性发育,以及其他抗逆反应中的具体作用和机制及研究进展进行了阐述。本文还对ROP蛋白在ABA、IAA、BR等植物激素信号传导过程中的调控作用及研究进展进行了阐述。本文对植物ROP蛋白研究过程中尚未解决的问题,例如不同的ROP蛋白在同一个信号通路中的作用为何如此不同,以及ROP是如何协调不同的信号通路以共同调控一个植物发育或者生理过程等问题进行了总结,并在此基础上对未来的研究方向进行了展望。展开更多
Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, i...Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.展开更多
The freshwater planarian is a powerful animal model for studying regeneration and stem cell activity in vivo. During regeneration, stem cells （neoblasts in planarian） migrated to the wounding edge to re-build missin...The freshwater planarian is a powerful animal model for studying regeneration and stem cell activity in vivo. During regeneration, stem cells （neoblasts in planarian） migrated to the wounding edge to re-build missing parts of the body. However, proteins involved in regulating cell migration during planarian regeneration have not been studied extensively. Here we report two small GTPase genes （Djrho2 and Djrho3） of Dugesiajaponica （strain Pek-1）. In situ hybridization results indicated that Djrho2 was expressed throughout the body with the exception of thc pharynx region while Djrho3 was specifically expressed along the gastro-vascular system. Djrho2 was largely expressed in neoblasts since its expression was sensitive to X-ray irradiation. In Djrho2-RNAi planarians, smaller anterior blastemas were observed in tail fragments during regeneration. Consistently, defective regeneration of visual nerve was detected by immunostairming with VC-1 antibody. These results suggested that Djrho2 is required for proper anterior regeneration in planairan. In contrast, no abnormality was observed after RNAi of Djrho3. We compared protein compositions of control and Djrho2-RNAi planarians using an optimized proteomic approach. Twenty-two up-regulated and 26 de-regulated protein spots were observed in the two-dimensional elec- trophoresis gels, and 17 proteins were successfully identified by Mass Spectrometry （MS） analysis. Among them, 6 actin-binding or cytoskeleton-related proteins were found de-expressed in Djrho2-RNAi animals, suggesting that abnormal cytoskeleton assembling and cell migration were likely reasons of defected regeneration.展开更多
The roles of Rho family guanosine triphosphatases(GTPases)of plants(ROPs)in modulating plant growth and development have been well characterized.However,little is known about the roles of ROP signaling pathways in reg...The roles of Rho family guanosine triphosphatases(GTPases)of plants(ROPs)in modulating plant growth and development have been well characterized.However,little is known about the roles of ROP signaling pathways in regulating plant autophagy and autophagosome formation.In this study,we identify a unique ROP signaling mechanism,which mediates developmental to autophagic transition under stress conditions in the model plant Arabidopsis.Loss-of-function mutants of ROP8 showed stress-induced hypersensitive phenotypes and compromised autophagic flux.Similar to other ROPs in the ROP/RAC family,ROP8 exhibits both plasma membrane and cytosolic punctate localization patterns.Upon autophagic induction,active ROP8 puncta colocalize with autophagosomal markers and are degraded inside the vacuole.In human cells,RalB,an RAS subfamily GTPase,engages its effector Exo84 for autophagosome assembly.However,a RalB counterpart is missing in the plant lineage.Intriguingly,we discovered that plant ROP8 promotes autophagy via its downstream effector Sec5.Live-cell super-resolution imaging showed that ROP8 and Sec5 reside on phagophores for autophagosome formation.Taken together,our findings highlight a previously unappreciated role of an ROP8-Sec5 signaling axis in autophagy promotion,providing new insights into how plants utilize versatile ROP signaling networks to coordinate developmental and autophagic responses depending on environmental changes.展开更多
Cell polarity operates across a broad range of spatial and temporal scales and is essential for specific biological functions of polarized cells.Tip growth is a special type of polarization in which a single and uniqu...Cell polarity operates across a broad range of spatial and temporal scales and is essential for specific biological functions of polarized cells.Tip growth is a special type of polarization in which a single and unique polarization site is established and maintained,as for the growth of root hairs and pollen tubes in plants.Extensive studies in past decades have demonstrated that the spatiotemporal localization and activity of Rho of Plants(ROPs),the only class of Rho GTPases in plants,are critical for tip growth.ROPs are switched on or off by different factors to initiate dynamic intracellular activities,leading to tip growth.Recent studies have also uncovered several feedback modules for ROP signaling.In this review,we summarize recent progress on ROP signaling in tip growth,focusing on molecular mechanisms that underlie the dynamic distribution and activity of ROPs in Arabidopsis.We also highlight feedback modules that control ROPmediated tip growth and provide a perspective for building a complex ROP signaling network.Finally,we provide an evolutionary perspective for ROP-mediated tip growth in Physcomitrella patens and during plant–rhizobia interaction.展开更多
Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human d...Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, recep- tor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiq- uitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on inves- tigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases＇ biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.展开更多
Tip growth is a special type of polarized growth in which a single and unique polarization site is established and maintained.Rho of Plants(ROP)proteins,which represent the only class of Rho GTPases in plants,regulate...Tip growth is a special type of polarized growth in which a single and unique polarization site is established and maintained.Rho of Plants(ROP)proteins,which represent the only class of Rho GTPases in plants,regulate tip growth.The dynamic and asymmetric distribution of ROPs is critical for the establishment and maintenance of tip growth,and requires at least one positive feedback loop,which is still elusive.Here,we report a positive feedback circuit essential for tip growth of root hairs,in which ROPs,ROP activators and effectors,and AGC1.5 subfamily kinases are interconnected by sequential oligomerization and phosphorylation.AGC1.5 subfamily kinases interact with and phosphorylate two guanine nucleotide exchange factors(GEFs)of ROPs,RopGEF4 and RopGEF10.They also interact with two ROP effectors,ICR2/RIP3 and MIDD1/RIP4,which bridge active ROPs with AGC1.5.Functional loss of the AGC1.5 subfamily kinases or ICR2 and MIDD1 compromised root hair growth due to reduced ROP signaling.We found that asymmetric targeting of RopGEF4 and RopGEF10 is controlled by AGC1.5-dependent phosphorylation.Interestingly,we discovered that the ROP effectors recruit AGC1.5 to active ROP domains at the plasma membrane during root hair growth and are critical for AGC1.5-dependent phosphorylation of RopGEFs.Given the large number of AGC kinases in plants,this positive feedback circuit may be a universal theme for plant cell polar growth.展开更多
基金supported by the TWU Department of Biologygrants from the TWU Research Enhancement Program+3 种基金Closing the Gaps programTargeted Research Funds programthe National Science Foundationthe National Institutes of Health
文摘Damage to neurons in the central nervous system often leads to a permanent loss of function due to several factors,including reduced capacity of axons to regenerate and an environment that inhibits axon regeneration because of disruption of myelin and the formation of a growth-refractory glial scar around the injury（Yoon and Tuszynski,2012）.
文摘With the support by the National Natural Science Foundation of China,a study by Prof.Zhu Yongqun’s(朱永群)research group from the Life Sciences Institute,Zhejiang University revealed that a conserved effector protein of bacterial MARTX toxins catalyzes N~ε-fatty acylation on the lysine residues in the C-
基金supported by the Natural Science Foundation of Jiangsu Province,No.BK20221377(to JG)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB180023(to JG)。
文摘Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.
基金Supported by:the National Basic Research Program of China(973 Program),No. 2007CB512705the Natural Science Foundation of Guangdong Province,No. 8451063201000193
文摘BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules related to Rho GTPases. OBJECTIVE： To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases, including Rho-A, Rac-1, collapsin response mediator protein 1 （CRMP-1）, and tubulin 133 （Tub/33） during rat hippocampus development. DESIGN, TIME AND SETTING- A non-randomized, controlled, animal experiment, based on different developmental stages of the rat hippocampus, was performed at the Guangdong Key Laboratory of Tissue Construction and Detection, Institute of Clinical Anatomy, Southern Medical University between December 2005 and July 2007. MATERIALS： Trizol reagent was purchased from Invitrogen, USA. RNA PCR kit （AMV） Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa, Japan. Unless otherwise specified, all other reagents were purchased from Sigma-Aldrich, USA. METHODS： Twenty-five Sprague Dawley rats were assigned to five groups （n = 5） according to developmental stages： embryonic （embryonic 15 days）, neonatal （postnatal 5 days）, juvenile （postnatal 1 month）, adult （postnatal 3 months）, and senile （postnatal 18 months）. MAIN OUTCOME MEASURES： Detection of mRNA expression of Rho-A, Rac-1, CRMP-1, and Tub β3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction. RESULTS： Hippocampal mRNA expression of Rho-A, as well as Rac-1, reached peak levels at embryonic, juvenile, and senile stages, and was relatively less during neonatal and adult stages. mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage. CRMP-1 mRNA expression levels were as follows： embryonic 〉 neonatal 〉 juvenile 〉 adult 〈 senile, while Tubβ3 mRNA expression was embryonic 〉 neonatal 〉 juvenile 〉 adult = senile. CONCLUSION： Rho-A and Rac-1 shared similar expression profiles, which demonstrated similar variations during the entire rat hippocampus developmental process. However, Rac-1 mRNA expression remained greater than Rho-A. Both CRMP-1 and Tubβ3 mRNA expression profiles gradually declined during hippocampal development from embryonic to adult stages. Tubβ3 mRNA expression arrested during the adult stage, and CRMP-1 mRNA expression increased during the senile stage.
文摘植物RHO相关蛋白GTPases(RHO-related GTPases of plants,ROPs)是广泛存在于植物中的一类信号转导G蛋白(又称GTP结合蛋白),其通过结合GDP或GTP在非活性和活性状态间进行切换,进而在细胞极性控制、形态发育、激素水平调控、逆境反应等诸多植物生命活动的信号转导过程中扮演重要的分子开关角色。本文对ROP蛋白的结构域及基于蛋白质结构分类进行了介绍,并对拟南芥、玉米、水稻和大麦中的ROP家族蛋白质进行了系统进化分析。分析结果表明,这些植物中的ROP蛋白根据蛋白质结构域组成可分为Ⅰ类(typeⅠ)和Ⅱ类(typeⅡ)两种类型,而根据蛋白质序列的保守性可将其在植物中的ROP蛋白划分为4个进化枝。本综述不但对ROP蛋白作为分子开关在细胞内调控各种信号通路的机制进行了叙述,还对ROP在花粉管、根毛及植物表皮铺盖细胞极性发育,以及其他抗逆反应中的具体作用和机制及研究进展进行了阐述。本文还对ROP蛋白在ABA、IAA、BR等植物激素信号传导过程中的调控作用及研究进展进行了阐述。本文对植物ROP蛋白研究过程中尚未解决的问题,例如不同的ROP蛋白在同一个信号通路中的作用为何如此不同,以及ROP是如何协调不同的信号通路以共同调控一个植物发育或者生理过程等问题进行了总结,并在此基础上对未来的研究方向进行了展望。
基金supported by National Natural Science Foundation of China Grant (No. 81303129)Beijing University of Chinese Medicine Grant (Project ID: 2016-jxs-548)
文摘Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.
基金supported by grants to W.W. from the National Natural Science Foundation of China (No.30670225)the Major Science Programs of China (No.2006CB943402)
文摘The freshwater planarian is a powerful animal model for studying regeneration and stem cell activity in vivo. During regeneration, stem cells （neoblasts in planarian） migrated to the wounding edge to re-build missing parts of the body. However, proteins involved in regulating cell migration during planarian regeneration have not been studied extensively. Here we report two small GTPase genes （Djrho2 and Djrho3） of Dugesiajaponica （strain Pek-1）. In situ hybridization results indicated that Djrho2 was expressed throughout the body with the exception of thc pharynx region while Djrho3 was specifically expressed along the gastro-vascular system. Djrho2 was largely expressed in neoblasts since its expression was sensitive to X-ray irradiation. In Djrho2-RNAi planarians, smaller anterior blastemas were observed in tail fragments during regeneration. Consistently, defective regeneration of visual nerve was detected by immunostairming with VC-1 antibody. These results suggested that Djrho2 is required for proper anterior regeneration in planairan. In contrast, no abnormality was observed after RNAi of Djrho3. We compared protein compositions of control and Djrho2-RNAi planarians using an optimized proteomic approach. Twenty-two up-regulated and 26 de-regulated protein spots were observed in the two-dimensional elec- trophoresis gels, and 17 proteins were successfully identified by Mass Spectrometry （MS） analysis. Among them, 6 actin-binding or cytoskeleton-related proteins were found de-expressed in Djrho2-RNAi animals, suggesting that abnormal cytoskeleton assembling and cell migration were likely reasons of defected regeneration.
基金supported by grants from the National Natural Science Foundation of China(31670179 and 91854201)the Research Grants Council of Hong Kong(CUHK14130716,14104716,14102417,14100818,14101219,C4012-16E,C4033-19E,C4002-17G,C4002-20W,R4005-18,and AOE/M-05/12)。
文摘The roles of Rho family guanosine triphosphatases(GTPases)of plants(ROPs)in modulating plant growth and development have been well characterized.However,little is known about the roles of ROP signaling pathways in regulating plant autophagy and autophagosome formation.In this study,we identify a unique ROP signaling mechanism,which mediates developmental to autophagic transition under stress conditions in the model plant Arabidopsis.Loss-of-function mutants of ROP8 showed stress-induced hypersensitive phenotypes and compromised autophagic flux.Similar to other ROPs in the ROP/RAC family,ROP8 exhibits both plasma membrane and cytosolic punctate localization patterns.Upon autophagic induction,active ROP8 puncta colocalize with autophagosomal markers and are degraded inside the vacuole.In human cells,RalB,an RAS subfamily GTPase,engages its effector Exo84 for autophagosome assembly.However,a RalB counterpart is missing in the plant lineage.Intriguingly,we discovered that plant ROP8 promotes autophagy via its downstream effector Sec5.Live-cell super-resolution imaging showed that ROP8 and Sec5 reside on phagophores for autophagosome formation.Taken together,our findings highlight a previously unappreciated role of an ROP8-Sec5 signaling axis in autophagy promotion,providing new insights into how plants utilize versatile ROP signaling networks to coordinate developmental and autophagic responses depending on environmental changes.
基金funded by the National Natural Science Foundation of China(32100295 to E.L.)the Natural Science Foundation of Shandong Province(ZR2021QC001 to E.L.).
文摘Cell polarity operates across a broad range of spatial and temporal scales and is essential for specific biological functions of polarized cells.Tip growth is a special type of polarization in which a single and unique polarization site is established and maintained,as for the growth of root hairs and pollen tubes in plants.Extensive studies in past decades have demonstrated that the spatiotemporal localization and activity of Rho of Plants(ROPs),the only class of Rho GTPases in plants,are critical for tip growth.ROPs are switched on or off by different factors to initiate dynamic intracellular activities,leading to tip growth.Recent studies have also uncovered several feedback modules for ROP signaling.In this review,we summarize recent progress on ROP signaling in tip growth,focusing on molecular mechanisms that underlie the dynamic distribution and activity of ROPs in Arabidopsis.We also highlight feedback modules that control ROPmediated tip growth and provide a perspective for building a complex ROP signaling network.Finally,we provide an evolutionary perspective for ROP-mediated tip growth in Physcomitrella patens and during plant–rhizobia interaction.
文摘Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, recep- tor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiq- uitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on inves- tigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases＇ biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.
基金This work is funded by National Natural Science Foundation of China(31625003,31271578,31871422 to Y.Z.,31771558 and 31970332 to S.L.)Yan Zhang's lab is partially supported by Tai-Shan Scholar program by Shandong Provincial Government.
文摘Tip growth is a special type of polarized growth in which a single and unique polarization site is established and maintained.Rho of Plants(ROP)proteins,which represent the only class of Rho GTPases in plants,regulate tip growth.The dynamic and asymmetric distribution of ROPs is critical for the establishment and maintenance of tip growth,and requires at least one positive feedback loop,which is still elusive.Here,we report a positive feedback circuit essential for tip growth of root hairs,in which ROPs,ROP activators and effectors,and AGC1.5 subfamily kinases are interconnected by sequential oligomerization and phosphorylation.AGC1.5 subfamily kinases interact with and phosphorylate two guanine nucleotide exchange factors(GEFs)of ROPs,RopGEF4 and RopGEF10.They also interact with two ROP effectors,ICR2/RIP3 and MIDD1/RIP4,which bridge active ROPs with AGC1.5.Functional loss of the AGC1.5 subfamily kinases or ICR2 and MIDD1 compromised root hair growth due to reduced ROP signaling.We found that asymmetric targeting of RopGEF4 and RopGEF10 is controlled by AGC1.5-dependent phosphorylation.Interestingly,we discovered that the ROP effectors recruit AGC1.5 to active ROP domains at the plasma membrane during root hair growth and are critical for AGC1.5-dependent phosphorylation of RopGEFs.Given the large number of AGC kinases in plants,this positive feedback circuit may be a universal theme for plant cell polar growth.
