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small gtpases and cilia

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Protein & Cell 2011年第3期2卷 13-25页

作者： Yujie Li Jinghua Hu Department of Nephrology and Hypertension Mayo ClinicRochesterMinnesotaUSA Translational PKD Center Mayo ClinicRochesterMinnesotaUSA Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMinnesotaUSA

small gtpases are key molecular switches that bind and hydrolyze GTP in diverse membrane-and cytoskeletonrelated cellular ***,mounting evidences have highlighted the role of various small gtpases,including the members in Arf/Arl,Rab,and Ran subfamilies,in cilia formation and *** 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 *** 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 *** 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.

关键词： small gtpase cilia ciliopathy

Fine-tuning cell organelle dynamics during mitosis by small gtpases

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Frontiers of Medicine 2022年第3期16卷 339-357页

作者： Zijian Zhang Wei Zhang Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Clinical Immunology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Institute of Cancer Stem Cell Dalian Medical UniversityDalian 116044China

During mitosis,the allocation of genetic material concurs with organelle transformation and *** coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression,cell fate determination,and organismal *** gtpases belonging to the Ras superfamily regulate various cell organelles during *** 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 *** discoveries shed light on the molecular properties of small gtpases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure *** 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.

关键词： small gtpase cell organelle mitosis

Inactivation of Cdc42 in embryonic brain results in hydrocephalus with ependymal cell defects in mice

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Protein & Cell 2013年第3期4卷 231-242页

作者： Xu Peng Qiong Lin Yang Liu Yixin Jin Joseph E.Druso Marc A.Antonyak Jun-Lin Guan Richard A.Cerione Department of Systems Biology and Translational Medicine College of MedicineTexas A&M Health Science CenterTempleTX 76504USA Department of Molecular Medicine Cornell UniversityIthacaNY 14853USA Department of Internal Medicine-Division of Molecular Medicine and Genetics and Department of Cell and Developmental Biology University of Michigan Medical SchoolAnn ArborMI 48109USA

The establishment of a polarized cellular morphology is essential for a variety of processes including neural tube morphogenesis and the development of the ***42 is a Ras-related gtpase that plays an essential role in controlling cell polarity through the regulation of the actin and microtubule cytoskeleton *** studies have shown that Cdc42 plays an indispensable role in telencephalon development in earlier embryo developmental stage(before E12.5).However,the functions of Cdc42 in other parts of brain in later embryo developmental stage or in adult brain remain ***,in order to address the role of Cdc42 in the whole brain in later embryo developmental stage or in adulthood,we used Cre/loxP technology to generate two lines of tissue-specific Cdc42-knock-out *** of Cdc42 was achieved in neuroepithelial cells by crossing Cdc42/flox mice with Nestin-Cre mice and resulted in hydrocephalus,causing death to occur within the postnatal *** analyses of the brains from these mice showed that ependymal cell differentiation was disrupted,resulting in aqueductal *** of Cdc42 in the cerebral cortex also induced obvious defects in interki-netic nuclear migration and *** further explore the role of Cdc42 in adult mice brain,we examined the effects of knocking-out Cdc42 in radial glial cells by crossing Cdc42/flox mice with human glial fi brillary acidic protein(GFAP)-Cre *** of Cdc42 in radial glial cells resulted in hydrocephalus and ependymal cell *** together,these results highlight the importance of Cdc42 for ependymal cell differentiation and maintaining,and suggest that these functions likely contribute to the essential roles played by Cdc42 in the development of the brain.

关键词： Cdc42 small gtpase neuron glial cell polarity development

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Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer

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Protein & Cell 2022年第11期13卷 825-841页

作者： Junru Feng Hui Lu Wenhao Ma Wenjing Tian Zhuan Lu Hongying Yang Yongping Cai Pengfei Cai Yuchen Sun Zilong Zhou Jiaqian Feng Jiazhong Deng Ying Shu Kun Qu Weidong Jia Ping Gao Huafeng Zhang Anhui Key Laboratory of Hepatopancreatobiliary Surgery Department of General SurgeryAnhui Provincial HospitalThe First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Hefei National Laboratory for Physical Sciences at Microscale The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Shenzhen People’s Hospital Second Clinical Medical College of Jinan UniversityFirst Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518000China Department of Pathology School of MedicineAnhui Medical UniversityHefei 230032China School of Medicine and Institutes for Life Sciences South China University of TechnologyGuangzhou 510006China

Metformin is currently a strong candidate anti-tumor agent in multiple ***,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor *** thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin ***,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in ***,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin *** DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer ***,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 *** study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.

关键词： CRISPR screen DOCK1 hepatocellular carcinoma metformin small gtpase

Structural basis for targeting BIG1 to Golgi apparatus through interaction of its DCB domain with Arl1

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Structural basis for targeting BIG1 to Golgi apparatus throu...

中国生物化学与分子生物学会2016年全国学术会议

作者： Rong Wang Zhijing Wang Tianlong Zhang Jianping Ding National Center for Protein Science Shanghai State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Shanghai Science Research Center Chinese Academy of Sciences

The ADP ribosylation factor(Arf)family small gtpases,including Arf,Arl and Sar proteins,are modulators of vesicular and lipid trafficking in cell membrane *** BIG1 belongs to the Sec7 domain-containing Arf GEFs,which functions mainly on the trans-Golgi to activate Arf proteins from the GDP-bound form to GTPbound ***1 may direct the BIG1to the trans-Golgi through interaction with the N-terminal region of BIG1,and then activate the Arf-dependent pathway in a

关键词： Arl1 BIG1 small gtpase GEF

Myosin-5a motor function is co-activated by two cargo adaptor proteins RILPL2 and melanophilin

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Myosin-5a motor function is co-activated by two cargo adapto...

中国生物化学与分子生物学会2019年全国学术会议暨学会成立四十周年

作者： Qing-Juan Cao Ning Zhang Rui Zhou Lin-Lin Yao Xiang-dong Li Group of Cell Motility and Muscle Contraction State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of Zoology Chinese Academy of Sciences University of Chinese Academy of Sciences

Vertebrate myosin-5 a is an ATP-utilizing processive motor associated with the actin network and responsible for the transport and localization of several vesicle cargoes. To transport cargo efficiently and prevent futile ATP hydrolysis, myosin-5 a motor function must be tightly regulated. The globular tail domain(GTD) of myosin-5 a not only functions as the inhibitory domain, but also serves as the binding site for a number of cargo adaptor proteins, including melanophilin(Mlph) and Rab-interacting lysosomal proteinlike 2(RILPL2). In this study, using various biochemical approaches, including ATPase, single-molecule motility, and GST pulldown assays and analytical ultracentrifugation, we demonstrate that the binding of both Mlph and RILPL2 to the GTD of myosin-5 a is required for the activation of myosin-5 a motor function under physiological ionic conditions. We also found that this activation is regulated by the small gtpase Rab36, a binding partner of RILPL2. In summary, our results indicate that RILPL2 is required for Mlphmediated activation of Myo5 a motor activity under physiological conditions and that Rab36 promotes this activation. We propose that Rab36 stimulates RILPL2 to interact with the myosin-5 a GTD;this interaction then induces the exposure of the Mlph-binding site in the GTD, thereby enabling Mlph to interact with the GTD and activate myosin-5 a motor activity.

关键词： allosteric regulation melanophilin melanosome molecular motor myosin small gtpase vesicle transport

The study of rice innate immunity with visual biotechnology

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The study of rice innate immunity with visual biotechnology

从植物科学到农业发展——2012全国植物生物学大会

作者： Ko Shimamoto Laboratory of Plant Molecular Genetics Nara Institute of Science and Technology8916-5 TakayamaIkoma 630-0101Japan

Visual biotechnology based on laser microscopy and fluorescent proteins becomes the state-of-the-art approach to study molecular mechanism in *** and blast fungus are ideal model organisms to understand the plant-microbe *** FRET sensor,we demonstrated that chitin,a major PAMP signal for rice innate immunity,was able to activate molecular switch OsRacl in *** also found that a novel OsRac1 interactor, Hop/Stila was associated with chitin receptor OsCERK1 in vivo and important for chitin-triggered immune responses and rice blast *** further revealed that Hop/Sti1 regulated the maturation and transport of OsCERKl in the endoplasmic reticulum (ER) in a complex with ***,the mature OsCERKl was transported via the trafficking system to the plasma membrane(PM) for signal *** of Hop/Sti1 and Hsp90 function reduces the efficiency of OsCERKl transport to the PM leading to a defect of in chitin-triggered defense and fungal *** the other hand, Pi-ta/AVR-Pita is a classic pathosystem to study effector-triggered immunity in *** demonstrated that Pi-ta was colocalized with AVR-Pita in the mitochondria and interacted with a mitochondrial protein ***,the visual biotechnologies provide insightful information on the signal transduction of rice innate immunity.

关键词： Innate Immunity small gtpase Chitin CERK1 Pi-ta AVR-Pita