A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit
- Yale School of Medicine, United States
- 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
Tabitha A Peterson
Christopher G Burd
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.
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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A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit
eLife 6:e24126.
https://doi.org/10.7554/eLife.24126
