title: A memory system of negative polarity cues prevents replicative aging.
abstract: 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.
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Meitinger
authors.affiliation: Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Khmelinskii
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, 67400 Illkirch Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Morlot
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Bahtiyar
authors.initials: B
authors.lastname: Kurtulmus
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Palani
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Amparo
authors.initials: A
authors.lastname: Andres-Pons
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hub
authors.affiliation: Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knop
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, 67400 Illkirch Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Charvin
authors.affiliation: Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany. Electronic address: g.pereira@dkfz.de.
authors.forename: Gislene
authors.initials: G
authors.lastname: Pereira
mesh_terms: D060049:Asymmetric Cell Division; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C000596183:Nba1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae