A memory system of negative polarity cues prevents replicative aging.
Fiche publication
Date publication
novembre 2014
Journal
Cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARVIN Gilles
Tous les auteurs :
Meitinger F, Khmelinskii A, Morlot S, Kurtulmus B, Palani S, Andres-Pons A, Hub B, Knop M, Charvin G, Pereira G
Lien Pubmed
Résumé
Cdc42 is a highly conserved master regulator of cell polarity. Here, we investigated the mechanism by which yeast cells never re-establish polarity at cortical sites (cytokinesis remnants [CRMs]) that have previously supported Cdc42-mediated growth as a paradigm to mechanistically understand how Cdc42-inhibitory polarity cues are established. We revealed a two-step mechanism of loading the Cdc42 antagonist Nba1 into CRMs to mark these compartments as refractory for a second round of Cdc42 activation. Our data indicate that Nba1 together with a cortically tethered adaptor protein confers memory of previous polarization events to translate this spatial legacy into a biochemical signal that ensures the local singularity of Cdc42 activation. "Memory loss" mutants that repeatedly use the same polarity site over multiple generations display nuclear segregation defects and a shorter lifespan. Our work thus established CRMs as negative polarity cues that prevent Cdc42 reactivation to sustain the fitness of replicating cells.
Mots clés
Asymmetric Cell Division, Cell Cycle Proteins, metabolism, Cell Polarity, Guanine Nucleotide Exchange Factors, metabolism, Membrane Proteins, metabolism, Saccharomyces cerevisiae, cytology, Saccharomyces cerevisiae Proteins, metabolism, cdc42 GTP-Binding Protein, Saccharomyces cerevisiae, metabolism
Référence
Cell. 2014 Nov 20;159(5):1056-1069