A Role for Leukemia‐associated RhoGEF in the Final Stages of Cytokinesis

Abstract

Mitosis requires the concerted effort of multiple RhoGEFs to properly undergo cytokinesis and complete cellular division. Here we show that Leukemia‐associated RhoGEF (LARG), a RhoA‐specific RGS‐RhoGEF, is required for abscission, the final stage of cytokinesis in which the intercellular membrane is cleaved between daughter cells. LARG co‐localizes with alpha‐tubulin in early mitosis followed by a translocation to the midzone and eventual co‐localization with RhoA at the midbody of the cytokinetic furrow. LARG translocates to particulate fractions during mitotic exit, paralleling that of Myosin 2, and returns to soluble fractions following completion of cytokinesis. Live cell imaging of HeLa cells siRNA depleted of LARG reveals a failure in abscission and retention of the intercellular bridge, resulting in a 6‐fold increase in abscission‐related apoptosis. In contrast to studies of other RhoGEFs, particularly Ect2 and GEF‐H1, LARG depletion does not result in cytokinetic furrow regression nor does its depletion affect internal mitotic timing. Abscission‐related apoptosis resulting from LARG depletion can be rescued by expression of siRNA‐resistant LARG. These results show that LARG is a novel and temporally distinct RhoGEF required for the completion of abscission.