The RhoGAP ARHGAP19 controls cytokinesis and chromosome segregation in T lymphocytes

Abstract

Small GTP-binding proteins of the Rho family orchestrate the cytoskeleton remodeling 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 uncharacterized protein, is predominantly expressed in hematopoietic cells and is a critical actor of T lymphocyte division. 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 with these phenotypes, we show that ARHGAP19 acts as a GAP for RhoA, and controls Citron and Myosin II recruitment to the plasma membrane of mitotic lymphocytes as well as Rock2-mediated phosphorylation of Vimentin, a critical determinant in stiffness and shape of lymphocytes. In addition to its effects on cell shape changes, silencing of ARHGAP19 in lymphocytes also impairs chromosome segregation.