1. Cell Biology
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The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells

  1. Anjali Teckchandani
  2. Jonathan A Cooper  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
Research Article
  • Cited 14
  • Views 2,223
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Cite this article as: eLife 2016;5:e17440 doi: 10.7554/eLife.17440

Abstract

Cell migration requires the cyclical assembly and disassembly of focal adhesions. Adhesion induces phosphorylation of focal adhesion proteins, including Cas (Crk-associated substrate/p130Cas/BCAR1). However, Cas phosphorylation stimulates adhesion turnover. This raises the question of how adhesion assembly occurs against opposition from phospho-Cas. Here we show that suppressor of cytokine signaling 6 (SOCS6) and Cullin 5, two components of the CRL5SOCS6 ubiquitin ligase, inhibit Cas-dependent focal adhesion turnover at the front but not rear of migrating epithelial cells. The front focal adhesions contain phospho-Cas which recruits SOCS6. If SOCS6 cannot access focal adhesions, or cullins or the proteasome are inhibited, adhesion disassembly is stimulated. This suggests that the localized targeting of phospho-Cas within adhesions by CRL5SOCS6 and concurrent cullin and proteasome activity provide a negative feedback loop, ensuring that adhesion assembly predominates over disassembly at the leading edge. By this mechanism, ubiquitination provides a new level of spatio-temporal control over cell migration.

Article and author information

Author details

  1. Anjali Teckchandani

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    No competing interests declared.
  2. Jonathan A Cooper

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    jcooper@fhcrc.org
    Competing interests
    Jonathan A Cooper, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8626-7827

Funding

National Institutes of Health (R01 GM109463)

  • Jonathan A Cooper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Publication history

  1. Received: May 1, 2016
  2. Accepted: September 21, 2016
  3. Accepted Manuscript published: September 22, 2016 (version 1)
  4. Version of Record published: November 2, 2016 (version 2)

Copyright

© 2016, Teckchandani & Cooper

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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