David Muriel D, Petit Dominique, Bertoglio Jacques
Inserm U749, Institut Gustave Roussy, 94805 Villejuif, France.
J Cell Sci. 2014 Jan 15;127(Pt 2):400-10. doi: 10.1242/jcs.135079. Epub 2013 Nov 20.
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.
Rho家族的小GTP结合蛋白协调细胞分裂所需的细胞骨架重塑事件。鸟嘌呤核苷酸交换因子（GEFs）和GTP酶激活蛋白（GAPs）促进Rho GTP酶在活性GTP结合构象和非活性GDP结合构象之间循环。我们报告称，ARHGAP19是一种先前未被表征的蛋白质，主要在造血细胞中表达，并且在T淋巴细胞分裂中起重要作用。淋巴细胞中ARHGAP19的过表达会延迟细胞伸长和胞质分裂。相反，ARHGAP19的沉默或GAP缺陷型突变体的表达会诱导有丝分裂细胞早熟伸长和分裂沟内陷，以及过度的膜泡形成。关于这些表型，我们表明ARHGAP19作为RhoA的GAP起作用，并控制citron和肌球蛋白II募集到有丝分裂淋巴细胞的质膜以及Rock2介导的波形蛋白磷酸化，这对于维持淋巴细胞的硬度和形状至关重要。除了对细胞形状的影响外，淋巴细胞中ARHGAP19的沉默还会损害染色体分离。
