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Scaffold-mediated gating of Cdc42 signaling flux

  1. Péter Rapali
  2. Romain Mitteau
  3. Craig Ronald Braun
  4. Aurèlie Massoni-Laporte
  5. Caner Ünlü
  6. Laure Bataille
  7. Floriane Saint Arramon
  8. Steven P Gygi
  9. Derek McCusker  Is a corresponding author
  1. University of Bordeaux, CNRS, France
  2. Harvard Medical School, United States
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Cite this article as: eLife 2017;6:e25257 doi: 10.7554/eLife.25257

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.

Article and author information

Author details

  1. Péter Rapali

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Romain Mitteau

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Craig Ronald Braun

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Aurèlie Massoni-Laporte

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Caner Ünlü

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0612-3111
  6. Laure Bataille

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Floriane Saint Arramon

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Steven P Gygi

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Derek McCusker

    European Institute of Chemistry and Biology, University of Bordeaux, CNRS, Pessac, France
    For correspondence
    mccusker@iecb.u-bordeaux.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1455-1711

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.

Reviewing Editor

  1. Mohan K Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: January 18, 2017
  2. Accepted: March 15, 2017
  3. Accepted Manuscript published: March 17, 2017 (version 1)
  4. Version of Record published: April 10, 2017 (version 2)

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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