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Elife. 2017 Mar 31;6. pii: e24126. doi: 10.7554/eLife.24126.

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

Author information

1
Department of Cell Biology, Yale School of Medicine, New Haven, United States.
2
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, 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.

KEYWORDS:

CDC25 protein phosphatase; arrestin; biochemistry; cell biology; endosome; retromer

PMID:
28362258
PMCID:
PMC5409824
DOI:
10.7554/eLife.24126
[Indexed for MEDLINE]
Free PMC Article

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