TY - JOUR T1 - A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis JF - bioRxiv DO - 10.1101/364786 SP - 364786 AU - Brian Hercyk AU - Julie Rich AU - Maitreyi Das Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/08/03/364786.abstract N2 - Cdc42 is activated by the GEFs Gef1 and Scd1 in fission yeast. While gef1 and scd1 mutants exhibit distinct phenotypes, the mechanism by which this occurs is unclear given that they activate the same GTPase. We report that Gef1 and Scd1 regulate each other to spatially modulate Cdc42 activity during polarized growth and cytokinesis. We find that Gef1 mediates Scd1 localization via the scaffold Scd2. At the division site this enables proper septum formation, and at the new cell end during interphase this enables the transition from monopolar to bipolar growth. Reciprocally, Scd1 restricts Gef1 localization, via actin, at the division site to facilitate cell separation, and to sites of polarized growth during interphase to maintain cell shape. Our findings reveal an elegant regulatory pattern in which Gef1 establishes new sites of Scd1-mediated Cdc42 activity, while Scd1 restricts Gef1 to functional sites. We propose that crosstalk between GEFs is a conserved mechanism that orchestrates Cdc42 activation during multiple processes.SUMMARY Cdc42 is precisely regulated by unknown mechanisms. Hercyk et al. report that the Cdc42 GEFs regulate each other to spatially control Cdc42 activation during polarized growth and cytokinesis. Elucidation of this crosstalk provides an insight into how multiple GEFs regulating the same GTPase play distinct roles during complex processes. ER -