In mitosis animal cells lose their adhesion to the surrounding surfaces, and become rounded. During mitotic exit they re-establish these adhesions, and at the same time physically contract and divide. How these competing processes are spatially segregated at the cell cortex remains mysterious. To address this question we define the specific effector pathways used by RhoA and Rac1 in mitotic cells. We demonstrate that the MKlp1-CYK4 centralspindlin complex is a GAP for Rac1 and not RhoA, and that CYK4 negatively regulates Rac1 and cell adhesion in mitosis. Cells expressing a CYK4 GAP mutant or a form of Rac1 unable to hydrolyze GTP have cytokinesis defects due to cell adhesion in the cleavage furrow region. These defects can be rescued by depletion of ARHGEF7 and PAK, Rac1-specific effector proteins required for cell adhesion. CYK4 GAP activity is therefore required for the spatial segregation of cell adhesion and cortical contraction during cytokinesis.
