1. Cell Biology
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The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane

  1. Nicholas R Weir
  2. Roarke A Kamber
  3. James S Martenson
  4. Vladimir Denic  Is a corresponding author
  1. Harvard University, United States
Research Article
  • Cited 32
  • Views 2,417
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Cite this article as: eLife 2017;6:e28507 doi: 10.7554/eLife.28507

Abstract

Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence.

Article and author information

Author details

  1. Nicholas R Weir

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Roarke A Kamber

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. James S Martenson

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Vladimir Denic

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    vdenic@mcb.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1982-7281

Funding

National Institutes of Health

  • Vladimir Denic

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

Reviewing Editor

  1. Ramanujan S Hegde, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: May 10, 2017
  2. Accepted: September 12, 2017
  3. Accepted Manuscript published: September 14, 2017 (version 1)
  4. Version of Record published: October 9, 2017 (version 2)

Copyright

© 2017, Weir 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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