title: The RhoGAP ARHGAP19 controls cytokinesis and chromosome segregation in T lymphocytes.
abstract: Small GTP-binding proteins of the Rho family orchestrate the cytoskeleton remodelling events required for cell division. Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) promote cycling of Rho GTPases between the active GTP-bound and the inactive GDP-bound conformations. We report that ARHGAP19, a previously uncharacterised protein, is predominantly expressed in hematopoietic cells and has an essential role in the division of T lymphocytes. Overexpression of ARHGAP19 in lymphocytes delays cell elongation and cytokinesis. Conversely, silencing of ARHGAP19 or expression of a GAP-deficient mutant induces precocious mitotic cell elongation and cleavage furrow ingression, as well as excessive blebbing. In relation to these phenotypes, we show that ARHGAP19 acts as a GAP for RhoA, and controls recruitment of citron and myosin II to the plasma membrane of mitotic lymphocytes as well as Rock2-mediated phosphorylation of vimentin, which is crucial to maintain the stiffness and shape of lymphocytes. In addition to its effects on cell shape, silencing of ARHGAP19 in lymphocytes also impairs chromosome segregation.
authors.affiliation: Inserm U749, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: Muriel D
authors.initials: MD
authors.lastname: David
authors.forename: Dominique
authors.initials: D
authors.lastname: Petit
authors.forename: Jacques
authors.initials: J
authors.lastname: Bertoglio
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D020090:Chromosome Segregation / Q000187:drug effects; D048749:Cytokinesis / Q000187:drug effects; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D024462:Myosin Type II / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D049468:Prometaphase / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C521098:ARHGAP19 protein, human; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014746:Vimentin; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024462:Myosin Type II; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D015739:Nocodazole
keywords: Cytokinesis; Lymphocytes; Rho GTPases; Rock; Vimentin