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
Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane-and cytoskeletonrelated cellular processes.Recently,mounting evidences have highlighted the role of various small GTPases,includ...Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane-and cytoskeletonrelated cellular processes.Recently,mounting evidences have highlighted the role of various small GTPases,including the members in Arf/Arl,Rab,and Ran subfamilies,in cilia formation and function.Once overlooked as an evolutionary vestige,the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases,now called ciliopathies.Here we review recent advances about the function of small GTPases in the context of cilia,and the correlation between the functional impairment of small GTPases and ciliopathies.Understanding of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes,and their potential as therapeutic targets.展开更多
During mitosis,the allocation of genetic material concurs with organelle transformation and distribution.The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression,ce...During mitosis,the allocation of genetic material concurs with organelle transformation and distribution.The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression,cell fate determination,and organismal homeostasis.Small GTPases belonging to the Ras superfamily regulate various cell organelles during division.Being the key regulators of membrane dynamics,the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases,such as cancer and Alzheimer’s disease.Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation.This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.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
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
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
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.
基金the National Institutes of Health grant 1R01DK090038 and the PKD Foundation Young Investigator Award 04YI09a to J.HJ.H.is also supported by FULK Career Development Award,Zell PKD Research Fund,Upjohn PKD Research Fund,and Early Career Development Award from Mayo Clinic.
文摘Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane-and cytoskeletonrelated cellular processes.Recently,mounting evidences have highlighted the role of various small GTPases,including the members in Arf/Arl,Rab,and Ran subfamilies,in cilia formation and function.Once overlooked as an evolutionary vestige,the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases,now called ciliopathies.Here we review recent advances about the function of small GTPases in the context of cilia,and the correlation between the functional impairment of small GTPases and ciliopathies.Understanding of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes,and their potential as therapeutic targets.
基金supported by the National Kcy R&D Program of China(Nos.2019YFA0110300 and 2017YFA0505600-04)the National Natural Science Foundation of China(Nos.81820108024 and 81630005)+1 种基金the Innovative Research Team in University of Ministry of Edueation of China(No.IRT-17R15)and the Natural Science Foundation of Guangdong(Nos.2016A030311038 and 2017A030313608).
文摘During mitosis,the allocation of genetic material concurs with organelle transformation and distribution.The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression,cell fate determination,and organismal homeostasis.Small GTPases belonging to the Ras superfamily regulate various cell organelles during division.Being the key regulators of membrane dynamics,the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases,such as cancer and Alzheimer’s disease.Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation.This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.
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.
