Journal
JOURNAL OF CELL SCIENCE
Volume 127, Issue 2, Pages 400-410Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.135079
Keywords
Rho GTPases; Cytokinesis; Lymphocytes; Rock; Vimentin
Categories
Funding
- INSERM
- Ligue Nationale Contre le Cancer (Equipe labellisee)
- Agence Nationale de la Recherche [BLAN06 2_135169]
- Ligue Nationale Contre le Cancer
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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.
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