1. Cell Biology
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Discrete spatial organization of TGFβ receptors couples receptor multimerization and signaling to cellular tension

  1. Joanna P Rys
  2. Christopher C DuFort
  3. David A Monteiro
  4. Michelle A Baird
  5. Juan A Oses-Prieto
  6. Shreya Chand
  7. Alma L Burlingame
  8. Michael W Davidson
  9. Tamara N Alliston  Is a corresponding author
  1. University of California, Berkeley, United States
  2. University of California, San Francisco, United States
  3. Florida State University, United States
Research Article
  • Cited 22
  • Views 2,329
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Cite this article as: eLife 2015;4:e09300 doi: 10.7554/eLife.09300

Abstract

Cell surface receptors are central to the cell's ability to generate coordinated responses to the multitude of biochemical and physical cues in the microenvironment. However, the mechanisms by which receptors enable this concerted cellular response remain unclear. To investigate the effect of cellular tension on cell surface receptors, we combined novel high-resolution imaging and single particle tracking with established biochemical assays to examine TGFβ signaling. We find that TGFβ receptors are discretely organized to segregated spatial domains at the cell surface. Integrin-rich focal adhesions organize TβRII around TβRI, limiting the integration of TβRII while sequestering TβRI at these sites. Disruption of cellular tension leads to a collapse of this spatial organization and drives formation of heteromeric TβRI/TβRII complexes and Smad activation. This work details a novel mechanism by which cellular tension regulates TGFβ receptor organization, multimerization, and function, providing new insight into the mechanisms that integrate biochemical and physical cues.

Article and author information

Author details

  1. Joanna P Rys

    University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher C DuFort

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David A Monteiro

    University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michelle A Baird

    National High Magnetic Field Laboratory, Department of Biological Science, Florida State University, Tallahassee, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Juan A Oses-Prieto

    Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shreya Chand

    Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Alma L Burlingame

    Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael W Davidson

    National High Magnetic Field Laboratory, Department of Biological Science, Florida State University, Tallahassee, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Tamara N Alliston

    University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, United States
    For correspondence
    tamara.alliston@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Johanna Ivaska, University of Turku, Finland

Publication history

  1. Received: June 8, 2015
  2. Accepted: November 4, 2015
  3. Accepted Manuscript published: December 10, 2015 (version 1)
  4. Version of Record published: January 19, 2016 (version 2)

Copyright

© 2015, Rys 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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