title: A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit.
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.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, United States.
authors.forename: Tie-Zhong
authors.initials: TZ
authors.lastname: Cui
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States.
authors.forename: Tabitha A
authors.identifier: 0000-0003-0780-5795
authors.initials: TA
authors.lastname: Peterson
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, United States.
authors.forename: Christopher G
authors.identifier: 0000-0003-1831-8706
authors.initials: CG
authors.lastname: Burd
mesh_terms: D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D020125:Mutation, Missense; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020666:ras-GRF1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C542351:CDC25 protein, S cerevisiae; C089990:PEP8 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020666:ras-GRF1; D010749:Phosphoprotein Phosphatases
keywords: CDC25 protein phosphatase; arrestin; biochemistry; cell biology; endosome; retromer