MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody

We have recently cloned a cDNA for a full-length form of MgcRacGAP. Here we show using anti-MgcRacGAP antibodies that, unlike other known GAPs for Rho family, MgcRacGAP localized to the nucleus in interphase, accumulated to t he mitotic spindle in metaphase, and was condensed in the midbody during cy tokinesis. Overexpression of an N-terminal deletion mutant resulted in the production of multinucleated cells in HeLa cells. This mutant lost the abil ity to localize in the mitotic spindle and midbody. MgcRacGAP was also foun d to bind alpha-, beta, and gamma -tubulins through its N-terminal myosin-l ike domain. These results indicate that MgcRacGAP dynamically moves during cell cycle progression probably through binding to tubulins and plays criti cal roles in cytokinesis, Furthermore, using a GAP-inactive mutant, we have shown that the GAP activity of MgcRacGAP is required for cytokinesis, sugg esting that inactivation of the Rho family of GTPases may be required for n ormal progression of cytokinesis.