RRC ID 70424
Author Salat-Canela C, Carmona M, Martín-García R, Pérez P, Ayté J, Hidalgo E.
Title Stress-dependent inhibition of polarized cell growth through unbalancing the GEF/GAP regulation of Cdc42.
Journal Cell Rep
Abstract 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 Sty1-kinase-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 Δsty1 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 of Cdc42 at cell tips, halting polarized growth during stress adaptation.
Volume 37(5)
Pages 109951
Published 2021-11-2
DOI 10.1016/j.celrep.2021.109951
PII S2211-1247(21)01428-5
PMID 34731607
MeSH Cell Polarity* Cell Proliferation* GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Gene Expression Regulation, Fungal Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism Oxidative Stress* Rho Guanine Nucleotide Exchange Factors / genetics Rho Guanine Nucleotide Exchange Factors / metabolism* Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces / growth & development Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction Time Factors cdc42 GTP-Binding Protein / genetics cdc42 GTP-Binding Protein / metabolism*
IF 8.109