Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significan...Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.展开更多
Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The...Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The major role of Rho GTPases, which is conserved in all eukaryotes, is to regulate the actin and microtubule cytoskeleton. Therefore theRhoGTPases are key regulators of neuronal morphology during development besides their canonical functions in actin cytoskeletal regulation, cell migration and cell cycle progression. Semaphorins are a family of secreted or transmembrane proteins, which function through their receptor plexins and/or neuropilins to act as the repulsive or attractive guidance cues for axons and dendrites. It has been demonstrated that the fully activetion of plexins appears to be dependent on the binding of RhoGTPases to theRhobinding domain (RBD) and Semaphorin to the extracellular region. Here, we summarize the functions of the small Rho GTPases in two well-studied vertebrate Semaphorins, Sema3Aand Sema4D;and the potential roles of the small Rho GTPases in some poorly-studied vertebrate Semaphorins Sema5A, Sema6Aand Sema7A. We also summarize the functions of different members of Ras family, R-Ras, M-Ras and Rap, in Semaphorin signalling pathways as well.展开更多
Reepithelialization of skin which comprises epidermis and dermis has not been fully elucidated due to the complexity of the participants as well as the interactions therein. In this study, the intrinsic roles and beha...Reepithelialization of skin which comprises epidermis and dermis has not been fully elucidated due to the complexity of the participants as well as the interactions therein. In this study, the intrinsic roles and behaviors of epidermis itself during wound closure on neonatal rat skin were explored by developing and utilizing a novel in vivo wound model, termed “shallow incisional wound” in which the injury of dermis was minimized. The shallow wounds were closed by 12 h postwounding (PW) by the migration of the wound-marginal epidermal sheets in which activated myosin light chain (p-MLC) was predominantly detected at the lateral plasma membrane of individual cells. By local administration of Rho-associated protein kinase (ROCK) inhibitor Y27632, p-MLC disappeared at the wound margin and wounds were not closed by 12 h PW. Inhibition of Rac 1 by NSC23766 also resulted in hold of wound closure by 12 h PW, though NSC23766 somewhat slowly acted on p-MLC expression. These results suggest that, without joining of dermis, epidermal cells have a potential ability of closing wounds by active epithelial sheet movement integrated by Rho family small GTPases-dependent extension and contraction of the individual cell bodies.展开更多
小G蛋白(small GTPases)是近年来细胞信号转导的研究热点,包括Ras、Rho、Rab、Arf和Ran等5个亚家族.植物中存在一种特殊的小G蛋白ROP(Rho-related GTPase from plants)是Rho家族成员,在调控细胞生长发育及植物防御反应体系的建立等方面...小G蛋白(small GTPases)是近年来细胞信号转导的研究热点,包括Ras、Rho、Rab、Arf和Ran等5个亚家族.植物中存在一种特殊的小G蛋白ROP(Rho-related GTPase from plants)是Rho家族成员,在调控细胞生长发育及植物防御反应体系的建立等方面起重要作用.在植物细胞中ROP存在两种形式,一种是与GTP结合的激活态,另一种是与GDP结合的非激活态,通过这种激活态与非激活态之间的转变,ROPs作为植物生长发育过程中重要的分子开关"参与调控多种信号转导过程.本文主要对国内外近年来有关小G蛋白的种类及其调节机制,以及植物小G蛋白ROP在花粉管生长、根毛发育、H2O2的产生、脱落酸(ABA)以及防御应答反应中的调节作用等方面的研究进展进行综述.展开更多
Rif(Rho in filopodia)作为Rho小G蛋白家族的一员在调节细胞骨架形态方面有多种作用,可以同时介导压力纤维(stress fibers)和丝状伪足(filopodia)结构的形成.为了进一步研究Rif分子的功能,通过蛋白质组学的方法在高表达内源性Rif蛋白的H...Rif(Rho in filopodia)作为Rho小G蛋白家族的一员在调节细胞骨架形态方面有多种作用,可以同时介导压力纤维(stress fibers)和丝状伪足(filopodia)结构的形成.为了进一步研究Rif分子的功能,通过蛋白质组学的方法在高表达内源性Rif蛋白的HeLa细胞中寻找其新的相互作用蛋白.通过分析,发现了Rif与输出蛋白5(exportin 5)等几个核质蛋白存在潜在的相互作用.实验证明,Rif与输出蛋白5的相互作用是核苷酸依赖性的,并且这种相互作用可以将细胞质中存在的输出蛋白5转运回细胞核内.这些发现揭示了小G蛋白Rif可能作为核质大分子运输载体的新功能.展开更多
Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the patho- genesis of severe dengue remains unclear. In this study, we showed that the Racl-microfilam...Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the patho- genesis of severe dengue remains unclear. In this study, we showed that the Racl-microfilament signal pathway was involved in the process of DENV serotype 2 （DENV2） infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Racl activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Racl promoted DENV2 entry but inhibited viral as- sembly, maturation and release. Our findings demonstrated that Racl plays an important role in the DENV2 life cycle by reg- ulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.展开更多
基金supported by the National Natural Science Foundation of China[81690264]the National Basic Research Program of China[2015CB932100,2017YFA0205600]the Innovation Team of the Ministry of Education[BMU20110263]。
文摘Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.
文摘Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The major role of Rho GTPases, which is conserved in all eukaryotes, is to regulate the actin and microtubule cytoskeleton. Therefore theRhoGTPases are key regulators of neuronal morphology during development besides their canonical functions in actin cytoskeletal regulation, cell migration and cell cycle progression. Semaphorins are a family of secreted or transmembrane proteins, which function through their receptor plexins and/or neuropilins to act as the repulsive or attractive guidance cues for axons and dendrites. It has been demonstrated that the fully activetion of plexins appears to be dependent on the binding of RhoGTPases to theRhobinding domain (RBD) and Semaphorin to the extracellular region. Here, we summarize the functions of the small Rho GTPases in two well-studied vertebrate Semaphorins, Sema3Aand Sema4D;and the potential roles of the small Rho GTPases in some poorly-studied vertebrate Semaphorins Sema5A, Sema6Aand Sema7A. We also summarize the functions of different members of Ras family, R-Ras, M-Ras and Rap, in Semaphorin signalling pathways as well.
文摘Reepithelialization of skin which comprises epidermis and dermis has not been fully elucidated due to the complexity of the participants as well as the interactions therein. In this study, the intrinsic roles and behaviors of epidermis itself during wound closure on neonatal rat skin were explored by developing and utilizing a novel in vivo wound model, termed “shallow incisional wound” in which the injury of dermis was minimized. The shallow wounds were closed by 12 h postwounding (PW) by the migration of the wound-marginal epidermal sheets in which activated myosin light chain (p-MLC) was predominantly detected at the lateral plasma membrane of individual cells. By local administration of Rho-associated protein kinase (ROCK) inhibitor Y27632, p-MLC disappeared at the wound margin and wounds were not closed by 12 h PW. Inhibition of Rac 1 by NSC23766 also resulted in hold of wound closure by 12 h PW, though NSC23766 somewhat slowly acted on p-MLC expression. These results suggest that, without joining of dermis, epidermal cells have a potential ability of closing wounds by active epithelial sheet movement integrated by Rho family small GTPases-dependent extension and contraction of the individual cell bodies.
文摘小G蛋白(small GTPases)是近年来细胞信号转导的研究热点,包括Ras、Rho、Rab、Arf和Ran等5个亚家族.植物中存在一种特殊的小G蛋白ROP(Rho-related GTPase from plants)是Rho家族成员,在调控细胞生长发育及植物防御反应体系的建立等方面起重要作用.在植物细胞中ROP存在两种形式,一种是与GTP结合的激活态,另一种是与GDP结合的非激活态,通过这种激活态与非激活态之间的转变,ROPs作为植物生长发育过程中重要的分子开关"参与调控多种信号转导过程.本文主要对国内外近年来有关小G蛋白的种类及其调节机制,以及植物小G蛋白ROP在花粉管生长、根毛发育、H2O2的产生、脱落酸(ABA)以及防御应答反应中的调节作用等方面的研究进展进行综述.
基金Supported by Program of Higher-level Talents of Inner Mongolia University(SPH-IMU,30105-125128)~~
文摘Rif(Rho in filopodia)作为Rho小G蛋白家族的一员在调节细胞骨架形态方面有多种作用,可以同时介导压力纤维(stress fibers)和丝状伪足(filopodia)结构的形成.为了进一步研究Rif分子的功能,通过蛋白质组学的方法在高表达内源性Rif蛋白的HeLa细胞中寻找其新的相互作用蛋白.通过分析,发现了Rif与输出蛋白5(exportin 5)等几个核质蛋白存在潜在的相互作用.实验证明,Rif与输出蛋白5的相互作用是核苷酸依赖性的,并且这种相互作用可以将细胞质中存在的输出蛋白5转运回细胞核内.这些发现揭示了小G蛋白Rif可能作为核质大分子运输载体的新功能.
基金supported by the National Key Programs on Basic Research of China (2011CB504703)the National Natural Science Foundations of China (81301435, 81471957, 81271839, 81401676)Beijing Natural Science Foundation (7144194)
文摘Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the patho- genesis of severe dengue remains unclear. In this study, we showed that the Racl-microfilament signal pathway was involved in the process of DENV serotype 2 （DENV2） infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Racl activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Racl promoted DENV2 entry but inhibited viral as- sembly, maturation and release. Our findings demonstrated that Racl plays an important role in the DENV2 life cycle by reg- ulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.
