PT  - JOURNAL ARTICLE
AU  - Brian S. Hercyk
AU  - Maitreyi E. Das
TI  - F-BAR Cdc15 Promotes Gef1-mediated Cdc42 Activation During Cytokinesis and Cell Polarization in <em>S. pombe</em>
AID  - 10.1101/552927
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 552927
4099  - http://biorxiv.org/content/early/2019/02/16/552927.short
4100  - http://biorxiv.org/content/early/2019/02/16/552927.full
AB  - 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, Schizosaccharomyces pombe. Cdc42 is activated by two partially redundant GEFs Gef1 and Scd1. Although both the 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 domain containing Cdc15 promotes Gef1 localization to its functional sites. We show that cdc15 promotes Gef1 association with the cytokinetic nodes to activate Cdc42 during ring assembly. Moreover, cdc15 phospho-mutants phenocopy polarity phenotypes of gef1 mutants. In a hypermorphic cdc15 mutant, Gef1 localizes precociously to the division site, and is readily detected at the cortical patches and the cell cortex. Correspondingly, the hypermorphic cdc15 mutant shows increased bipolarity during interphase and precocious Cdc42 activation at the division site during cytokinesis. Finally, loss of gef1 in hypermorphic cdc15 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. Taken together our data indicates that Cdc15 promotes Cdc42 activation specifically via Gef1 localization to the division site to facilitate proper cytokinesis and to the cell cortex to promote bipolarity.