Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and IQGAP-related proteins

Cytokinesis in eukaryotic organisms is under the control of small GTP-bindi ng proteins, although the underlying molecular mechanisms are not fully und erstood. Cortexillins are actin-binding proteins whose activity is crucial for cytokinesis in Dictyostelium. Here we show that the IQGAP-related and R ac1-binding protein DGAP1 specifically interacts with the C-terminal, actin -bundling domain of cortexillin I. Like cortexillin I, DGAP1 is enriched in the cortex of interphase cells and translocates to the cleavage furrow dur ing cytokinesis. The activated form of the small GTPase Rac1A recruits DGAP 1 into a quaternary complex with cortexillin I and II. In DGAP1(-) mutants, a complex can still be formed with a second IQGAP-related protein, GAPA. T he simultaneous elimination of DGAP1 and GAPA, however, prevents complex fo rmation and localization of the cortexillins to the cleavage furrow. This l eads to a severe defect in cytokinesis, which is similar to that found in c ortexillin I/II double-null mutants. Our observations define a novel and fu nctionally significant signaling pathway that is required for cytokinesis.