Editors' ChoiceCell Biology

Mothers tell daughters to wait for a mate

Sci. Signal.  31 Mar 2015:
Vol. 8, Issue 370, pp. ec77
DOI: 10.1126/scisignal.aab2071

How long the budding yeast Saccharomyces cerevisiae waits to divide depends on whether cells are exposed to the mating pheromone α-factor and the concentration of and duration of exposure. High concentrations of α-factor induce cell cycle arrest in G1 by stimulating activity of the mitogen-activated protein kinase (MAPK) Fus3, which activates the Cdk inhibitor Far1. Because MAPK signaling also induces expression of FAR1, Far1 accumulates in cells exposed to concentrations of α-factor below that which triggers arrest, thus resulting in G1 delay. Doncic et al. report that when cells were arrested in G1 by application of a high concentration of α-factor, most Far1 localized to the cytoplasm, with only a small amount (about 10% of total Far1 in each cell) localized to the nucleus. Upon complete withdrawal of α-factor, cells reentered the cell cycle, and nuclear Far1 was rapidly degraded, but cytoplasmic Far1 persisted and was transmitted to daughter cells. Mother cells that were released from mitotic arrest in medium containing a low concentration of α-factor passed on more cytoplasmic Far1 to their daughters than mothers that were released in medium containing no α-factor. The amount of Far1 inherited by a daughter cell positively correlated with mating efficiency and with the length of time it took the daughter to progress through G1. Photobleaching experiments indicated that there was little exchange of Far1 between the cytoplasm and nucleus, implying that the cytoplasmic pool of Far1 was stable. Cdc24 is a cytosolic guanine nucleotide exchange factor that binds Far1, and various experiments indicated that Cdc24 anchored Far1 in the cytoplasm. In cells with FAR1 mutations that reduced Far1-Cdc24 binding, Far1 was less abundant, less heritable, and less able to mediate G1 delay intergenerationally. Yeast must choose between waiting for a mating partner and committing to cell division, and this mechanism allows the length of the G1 pause to vary according to past pheromone exposure. Abundant cytoplasmic Far1 indicates that finding a mate is likely, thus lengthening the G1 pause. The absence of mating pheromone when the mother cell budded means that finding a mate is unlikely, so the daughter should commit to mitosis instead of pausing in G1 to wait for a mate.

A. Doncic, O. Atay, E. Valk, A. Grande, A. Bush, G. Vasen, A. Colman-Lerner, M. Loog, J. M. Skotheim, Compartmentalization of a bistable switch enables memory to cross a feedback-driven transition. Cell 160, 1182–1195 (2015). [PubMed]

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