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The scaffold protein Ste5 directly controls a switch-like mating decision in yeast


Evolution has resulted in numerous innovations that allow organisms to increase their fitness by choosing particular mating partners, including secondary sexual characteristics, behavioural patterns, chemical attractants and corresponding sensory mechanisms1. The haploid yeast Saccharomyces cerevisiae selects mating partners by interpreting the concentration gradient of pheromone secreted by potential mates through a network of mitogen-activated protein kinase (MAPK) signalling proteins2,3. The mating decision in yeast is an all-or-none, or switch-like, response that allows cells to filter weak pheromone signals, thus avoiding inappropriate commitment to mating by responding only at or above critical concentrations when a mate is sufficiently close4. The molecular mechanisms that govern the switch-like mating decision are poorly understood. Here we show that the switching mechanism arises from competition between the MAPK Fus3 and a phosphatase Ptc1 for control of the phosphorylation state of four sites on the scaffold protein Ste5. This competition results in a switch-like dissociation of Fus3 from Ste5 that is necessary to generate the switch-like mating response. Thus, the decision to mate is made at an early stage in the pheromone pathway and occurs rapidly, perhaps to prevent the loss of the potential mate to competitors. We argue that the architecture of the Fus3–Ste5–Ptc1 circuit generates a novel ultrasensitivity mechanism, which is robust to variations in the concentrations of these proteins. This robustness helps assure that mating can occur despite stochastic or genetic variation between individuals. The role of Ste5 as a direct modulator of a cell-fate decision expands the functional repertoire of scaffold proteins beyond providing specificity and efficiency of information processing5,6. Similar mechanisms may govern cellular decisions in higher organisms and be disrupted in cancer.

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Figure 1: Switch-like shmooing in yeast requires the Fus3–Ste5 interaction.
Figure 2: Levels of the Fus3–Ste5 complex are determined by the Ste5 phosphorylation state.
Figure 3: A novel form of ultrasensitivity explains the switch-like mating decision.
Figure 4: Experimental validation of model predictions.


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We thank J. Ferrell Jr, W. Lim, M. Babu, E. Stefan, C. Landry, F.-X. Campbell-Valois and E. Levy for comments on the manuscript; W. Lim and J. Vogel for providing plasmids and yeast strains; N. Paquin for assistance with the in vitro kinase assay; and J. Ollivier, O. Dushek and our laboratory members for discussions. This work was supported by grants from the Canadian Institutes of Health Research (MOP-GMX-152556) and a Canada Research Chair in Integrative Genomics to S.W.M. P.S.S. was supported by a Canada Research Chair in Systems Biology and currently holds a Scottish Universities Life Sciences Alliance Professorship, also in systems biology.

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Authors and Affiliations



M.K.M. and S.W.M. planned and designed experiments; M.K.M. performed experiments; V.S. and P.S.S. planned and V.S. performed the mathematical modelling; M.K.M., S.W.M., V.S. and P.S.S. analysed the results; M.K.M., V.S., P.S.S. and S.W.M. wrote the manuscript.

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Correspondence to Peter S. Swain or Stephen W. Michnick.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Material and Methods, Supplementary Figures 1-31 with legends, Supplementary Tables 1-3 and Supplementary References. (PDF 8014 kb)

Supplementary Movie 1

This movie file shows axial Budding in the absence of α-factor stimulus. (AVI 2664 kb)

Supplementary Movie 2

This movie file shows bipolar Budding in response to 0.1μM of α-factor stimulus. (AVI 1776 kb)

Supplementary Movie 3

This movie file shows shmooing in response to 1.0μM of α-factor stimulus. (AVI 2727 kb)

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Malleshaiah, M., Shahrezaei, V., Swain, P. et al. The scaffold protein Ste5 directly controls a switch-like mating decision in yeast. Nature 465, 101–105 (2010).

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