p190RhoGAP negatively regulates Rho activity at the cleavage furrow of mitotic cells

Abstract

Previous studies demonstrated that p190RhoGAP (p190) negatively affects cytokinesis in a Rho-GAP-dependent manner, suggesting that regulation of Rho may be a critical mechanism of p190 action during cytokinesis. P190 localizes to the cleavage furrow (CF) of dividing cells, and its levels decrease during late mitosis by an ubiquitin-mediated mechanism, consistent with the hypothesis that high RhoGTP levels are required for completion of cytokinesis. To determine whether RhoGTP levels in the CF are affected by p190 and to define the phase(s) of cytokinesis in which p190 is involved, we used FRET analysis alone or in combination with time lapse microscopy. In normal cell division activated Rho accumulated at the cell equator in early anaphase and in the contractile ring, where it co-localized with p190. Real-time movies revealed that cells expressing elevated levels of p190 exhibited multiple cycles of abnormal CF site selection and ingression/regression, which resulted in failed or prolonged cytokinesis. This was accompanied by mislocalization of active Rho at the aberrant CF sites. Quantified data revealed that in contrast to ECT2 and dominate negative p190 (Y1283Ap190), which resulted in hyper-activated Rho, Rho activity in the CF was reduced by wild type p190 in a dose-dependent manner. These results suggest that p190 regulates cytokinesis through modulation of Rho-GTP levels, thereby affecting CF specification site selection and subsequent ring contraction.

An RNA-zipcode-independent mechanism that localizesDia1mRNA to the perinuclear ER through interactions between Dia1 nascent peptide and Rho–GTP

“…The first model suggests that Dia1 nascent peptide interacts with Rho-GTP, which is bound to the ER membrane, thereby tethering the mRNA-ribosome complex on the ER. This is supported by the observations that Rho can bind to membrane structures, including the ER (Cussac et al, 1996;Ridley, 2006), and that RhoA can be enriched and activated in the perinuclear region of a variety of cell types (Gadea et al, 2007;Liu and Horowitz, 2006;Picard et al, 2009;Su et al, 2009) (Fig. 7F-H).…”

A complex of p190RhoGAP and anillin modulates RhoGTP and the cytokinetic furrow in human cells

“…6A,A9). That MLC II is downstream of p190 is further emphasized by the fact that the inability to complete cytokinesis due to p190 overexpression (and decreased RhoA-GTP levels) (Mikawa et al, 2008;Su et al, 2003;Su et al, 2009) can be rescued with a constitutively active MLC II. Fig.…”

Cycling around cell–cell adhesion with Rho GTPase regulators

“…Thus, the same regulatory unit (e.g. ECT2, MgcRacGAP and p190B) is able to regulate the interplay between Rac1 and RhoA in the contractile events that take place at the cleavage furrow or at junctions (Su et al, 2009;Ratheesh et al, 2012).…”