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Cell. 2014 Nov 20;159(5):1056-1069. doi: 10.1016/j.cell.2014.10.014. Epub 2014 Nov 13.

A memory system of negative polarity cues prevents replicative aging.

Author information

1
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
2
Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
3
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, 67400 Illkirch Cedex, France.
4
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
5
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.

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.

PMID:
25416945
DOI:
10.1016/j.cell.2014.10.014
[Indexed for MEDLINE]
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