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

• Published in: Cell reports (Cambridge) 2021-11, Vol.37 (5), p.109951-109951, Article 109951
• Main Authors: Salat-Canela, Clàudia, Carmona, Mercè, Martín-García, Rebeca, Pérez, Pilar, Ayté, José, Hidalgo, Elena
• Format: Article
• Language: English
• Subjects: Cdc42; cdc42 GTP-Binding Protein - genetics; cdc42 GTP-Binding Protein - metabolism; Cell Polarity; Cell Proliferation; cell size; GAP; GEF; Gene Expression Regulation, Fungal; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Oxidative Stress; Rga3; Rga6; Rho Guanine Nucleotide Exchange Factors - genetics; Rho Guanine Nucleotide Exchange Factors - metabolism; Scd1; Schizosaccharomyces - enzymology; Schizosaccharomyces - genetics; Schizosaccharomyces - growth & development; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Signal Transduction; stress response; Sty1; Time Factors
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109951

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. [Display omitted] •Oxidative stress causes Sty1-kinase-dependent inactivation of Cdc42 at cell poles•The GAPs Rga3/6 and the GEF Gef1 are direct targets of Sty1 kinase•Increased GAP activity at the cell poles mediates Cdc42 depolarization upon stress•Gef1 delocalization from cell tips promotes stress-dependent Cdc42 inactivation MAP kinases allow eukaryotic organisms to cope with environmental challenges. The fission yeast MAP kinase Sty1 couples stress signals with the Cdc42 polarity module, leading to the inhibition of polarized cell growth. Salat-Canela et al. decipher the molecular mechanism downstream of Sty1 that mediates the Cdc42 depolarization response.