F-BAR Cdc15 Promotes Cdc42 Activation During Cytokinesis and Cell Polarization in

Cdc42, a Rho-family GTPase, is a master regulator of cell polarity. Recently, it has been shown that Cdc42 also facilitates proper cytokinesis in the fission yeast Cdc42 is activated by two partially redundant GEFs, Gef1 and Scd1. Although both GEFs activate Cdc42, their deletion mutants display distinct phenotypes, indicating that they are differentially regulated by an unknown mechanism. During cytokinesis, Gef1 localizes to the division site and activates Cdc42 to initiate ring constriction and septum ingression. Here, we report that the F-BAR protein Cdc15 promotes Gef1 localization to its functional sites. We show that promotes Gef1 association with cortical puncta at the incipient division site to activate Cdc42 during ring assembly. Moreover, phospho-mutants phenocopy the polarity phenotypes of mutants. In a hypermorphic mutant, Gef1 localizes precociously to the division site and is readily detected at the cortical patches and the cell cortex. Correspondingly, the hypermorphic mutant shows increased bipolarity during interphase and precocious Cdc42 activation at the division site during cytokinesis. Finally, loss of in hypermorphic mutants abrogates the increased bipolarity and precocious Cdc42 activation phenotype. We did not see any change in the localization of the other GEF Scd1 in a Cdc15-dependent manner. Our data indicate that Cdc15 facilitates Cdc42 activation at the division site during cytokinesis at the cell cortex to promote bipolarity and this is mediated by promoting Gef1 localization to these sites.