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

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• dc.contributor.author Salat Canela, Clàudia, 1989-
• dc.contributor.author Carmona, Mercè
• dc.contributor.author Martín-García, Rebeca
• dc.contributor.author Pérez, Pilar
• dc.contributor.author Ayté del Olmo, José
• dc.contributor.author Hidalgo Hernando, Elena
• dc.date.accessioned 2022-01-18T06:53:31Z
• dc.date.available 2022-01-18T06:53:31Z
• dc.date.issued 2021
• dc.description.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.
• dc.description.sponsorship This work is supported by the Ministerio de Ciencia, Innovación y Universidades (Spain), PLAN E , and FEDER (grant PGC2018-093920-B-I00 to E.H., PGC2018-097248-B-I00 to J.A., and PGC2018-098924-B-100 to P.P.). The Oxidative Stress and Cell Cycle group is also supported by Generalitat de Catalunya (Spain) ( 2017-SGR-539 ) and Unidad de Excelencia María de Maeztu , funded by the AEI (Spain) (grant CEX2018-000792-M ). P.P. is also supported by Junta de Castilla y León (Escalera de la Excelencia) (grant CLU-2017-03 ). C.S.-C. was recipient of a María de Maeztu predoctoral fellowship from the Ministerio de Economía y Competitividad (Spain).
• dc.format.mimetype application/pdf
• dc.identifier.citation Salat-Canela C, Carmona M, Martín-García R, Pérez P, Ayté J, Hidalgo E. Stress-dependent inhibition of polarized cell growth through unbalancing the GEF/GAP regulation of Cdc42. Cell Rep. 2021;37(5):109951. DOI: 10.1016/j.celrep.2021.109951
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2021.109951
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/52247
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2021;37(5):109951
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-093920-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-097248-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-098924-B-100
• dc.rights © 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cdc42
• dc.subject.keyword GAP
• dc.subject.keyword GEF
• dc.subject.keyword Rga3
• dc.subject.keyword Rga6
• dc.subject.keyword Scd1
• dc.subject.keyword Sty1
• dc.subject.keyword Cell polarity
• dc.subject.keyword Cell size
• dc.subject.keyword Stress response
• dc.title Stress-dependent inhibition of polarized cell growth through unbalancing the GEF/GAP regulation of Cdc42
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion