Cell-to-cell variability in the yeast pheromone response: Cytoplasmic microtubule function stabilizes signal generation and promotes accurate fate choice

Pesce, Gustavo and Zdraljevic, Stefan and Bush, Alan and Repetto, Victoria and Peria, William and Yu, Richard C. and Colman-Lerner, Alejandro and Brent, Roger (2016) Cell-to-cell variability in the yeast pheromone response: Cytoplasmic microtubule function stabilizes signal generation and promotes accurate fate choice. bioRxiv (093195). (Submitted)

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Abstract

In a companion paper, we carried out a high-throughput screen to identify genes that suppressed cell-to-cell variability in signaling in yeast. Two genes affected cytoplasmic microtubules that can connect the nucleus to a signaling site on the membrane. Here, we show that microtubule perturbations that affected polymerization and depolymerization, membrane attachment, and force generation increased variability. For some perturbations, "outlier" cells drove the increased variability. Bypass experiments that activated the PRS ectopically at downstream points indicated that microtubule-dependent processes might stabilize the membrane-recruited scaffold protein Ste5. The variability caused by microtubule perturbations required the MAP kinase Fus3. Microtubule perturbations hindered stable scaffold formation and decreased the accuracy of a polarity-dependent fate choice. Our experiments suggest that membrane-attached microtubules stabilize signaling by scaffold-bound Fus3, and are consistent with a model in which signaling irregularities from changes in microtubule function are amplified by cross-stimulatory feedbacks among PRS proteins. The fact that microtubule perturbations also cause aberrant fate and polarity decisions during embryonic development and cancer initiation suggests that similar variation-reducing processes might also operate in metazoans.

Item Type:	Article or Abstract
DOI:	10.1101/093195
Grant Numbers:	R01 GM097479, R01 GM086615, P50 HG002370
Fred Hutch Divisions:	Basic Sciences
Depositing User:	Ann Marie Clark
Date Deposited:	12 Dec 2016 19:42
Last Modified:	12 Dec 2016 19:42
URI:	http://authors.fhcrc.org/id/eprint/1198

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