A memory system of negative polarity cues prevents replicative aging
Summary 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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 20, 2014
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| In: |
Cell
Year: 2014, Volume: 159, Issue: 5, Pages: 1056-1069 |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2014.10.014 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.cell.2014.10.014 Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S0092867414013026 
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| Author Notes: | Franz Meitinger, Anton Khmelinskii, Sandrine Morlot, Bahtiyar Kurtulmus, Saravanan Palani, Amparo Andres-Pons, Birgit Hub, Michael Knop, Gilles Charvin, and Gislene Pereira |
| Summary: | Summary 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. |
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| Item Description: | Gesehen am 22.05.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2014.10.014 |