Scaffold-mediated gating of Cdc42 signaling flux
- University of Bordeaux, CNRS, France
- Harvard Medical School, United States
Abstract
Scaffold proteins modulate signaling pathway activity spatially and temporally. In budding yeast, the scaffold Bem1 contributes to polarity axis establishment by regulating the GTPase Cdc42. While different models have been proposed for Bem1 function, there is little direct evidence for an underlying mechanism. Here, we find that Bem1 directly augments the Guanine Exchange Factor (GEF) activity of Cdc24. Bem1 also increases GEF phosphorylation by the p21-activated kinase (PAK), Cla4. Phosphorylation abrogates the scaffold-dependent stimulation of GEF activity, rendering Cdc24 insensitive to additional Bem1. Thus, Bem1 stimulates GEF activity in a reversible fashion, contributing to signaling flux through Cdc42. The contribution of Bem1 to GTPase dynamics was borne-out by in vivo imaging: active Cdc42 was enriched at the cell pole in hypophosphorylated cdc24 mutants, while hyperphosphorylated cdc24 mutants that were resistant to scaffold stimulation displayed a deficit in active Cdc42 at the pole. These findings illustrate the self-regulatory properties that scaffold proteins confer on signaling pathways.
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Funding
Centre National de la Recherche Scientifique
- Derek McCusker
Agence Nationale de la Recherche (ANR-13-BSV2-0015-01)
- Derek McCusker
Regional Council of Aquitaine (2012 13 01 012)
- Derek McCusker
Regional Council of Aquitaine (2015-1R30113)
- Derek McCusker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Rapali et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Scaffold-mediated gating of Cdc42 signaling flux
eLife 6:e25257.
https://doi.org/10.7554/eLife.25257
