A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit

  1. Tie-Zhong Cui
  2. Tabitha A Peterson
  3. Christopher G Burd  Is a corresponding author
  1. Yale School of Medicine, United States
  2. University of Iowa, United States

Abstract

We describe a regulatory mechanism that controls the activity of retromer, an evolutionarily conserved sorting device that orchestrates cargo export from the endosome. A spontaneously arising mutation that activates the yeast (Saccharomyces cerevisiae) CDC25 family phosphatase, Mih1, results in accelerated turnover of a subset of endocytosed plasma membrane proteins due to deficient sorting into a retromer-mediated recycling pathway. Mih1 directly modulates the phosphorylation state of the Vps26 retromer subunit; mutations engineered to mimic these states modulate the binding affinities of Vps26 for a retromer cargo, resulting in corresponding changes in cargo sorting at the endosome. The results suggest that a phosphorylation-based gating mechanism controls cargo selection by yeast retromer, and they establish a functional precedent for CDC25 protein phosphatases that lies outside of their canonical role in regulating cell cycle progression.

Article and author information

Author details

  1. Tie-Zhong Cui

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tabitha A Peterson

    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0780-5795
  3. Christopher G Burd

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    For correspondence
    christopher.burd@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1831-8706

Funding

National Institutes of Health (GM061221)

  • Christopher G Burd

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

Reviewing Editor

  1. Suzanne R Pfeffer, Stanford University School of Medicine, United States

Publication history

  1. Received: December 9, 2016
  2. Accepted: March 30, 2017
  3. Accepted Manuscript published: March 31, 2017 (version 1)
  4. Version of Record published: April 28, 2017 (version 2)

Copyright

© 2017, Cui 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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  1. Tie-Zhong Cui
  2. Tabitha A Peterson
  3. Christopher G Burd
(2017)
A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit
eLife 6:e24126.
https://doi.org/10.7554/eLife.24126

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