Stress-dependent inhibition of polarized cell growth through unbalancing the GEF/GAP regulation of Cdc42

Cdc42 GTPase rules cell polarity and growth in fission yeast. It is negatively and positively regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), respectively. Active Cdc42-GTP localizes to the poles, where it associates with numerous proteins constituting the polarity module. However, little is known about its downregulation. We describe here that oxidative stress causes Sty1kinase-dependent Cdc42 inactivation at cell poles. Both the amount of active Cdc42 at tips and cell length inversely correlate with Sty1 activity, explaining the elongated morphology of Dsty1 cells. We have created stress-blinded cell poles either by eliminating two Cdc42 GAPs or through the constitutive tethering of Gef1 to cell tips, and we biochemically demonstrate that the GAPs Rga3/6 and the GEF Gef1 are direct substrates of Sty1. We propose that phosphorylation of Rga3/6 and Gef1 mediates the Sty1-dependent inhibition

Automated summary

Cdc42 GTPase regulates cell polarity and growth in fission yeast through positive and negative regulation by GAPs and GEFs. Oxidative stress triggers Sty1 kinase-dependent inactivation of Cdc42 at cell poles, affecting cell morphology. The phosphorylation of Rga3/6 and Gef1 by Sty1 is proposed to mediate Sty1-dependent inhibition.