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PMID: 24643499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RME-8 coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation.

Journal of cell science ·Vol. 127 ·No. Pt 9 ·2014-05-01 ·Pages 2053-70

Freeman CL, Hesketh G, Seaman MN

Abstract

Retromer is a vital element of the endosomal protein sorting machinery and comprises two subcomplexes that operate together to sort membrane proteins (cargo) and tubulate membranes. Tubules are formed by a dimer of sorting nexins, a key component of which is SNX1. Cargo selection is mediated by the VPS35-VPS29-VPS26 trimer, which additionally recruits the WASH complex through VPS35 binding to the WASH complex subunit FAM21. Loss of function of the WASH complex leads to dysregulation of endosome tubulation, although it is unclear how this occurs. Here, we show that FAM21 also binds to the SNX1-interacting DNAJ protein RME-8. Loss of RME-8 causes altered kinetics of SNX1 membrane association and a pronounced increase in highly branched endosomal tubules. Building on previous observations from other laboratories, we show that these tubules contain membrane proteins that are dependent upon WASH complex activity for their localization to the plasma membrane. Therefore, we propose that the interaction between RME-8 and the WASH complex provides a means to coordinate the activity of the WASH complex with the membrane-tubulating function of the sorting nexins at sites where retromer-mediated endosomal protein sorting occurs.

Keywords
Endosome tubule RME-8 Retromer SNX WASH complex
MeSH Terms
Blotting, Western Electrophoresis, Polyacrylamide Gel Endosomes/metabolism HeLa Cells Humans Immunoprecipitation Microfilament Proteins/genetics,metabolism Microscopy, Fluorescence Molecular Chaperones/genetics,metabolism
Chemicals
DNAJC13 protein, human Microfilament Proteins Molecular Chaperones WASH protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Freeman Caroline L
University of Cambridge, Cambridge Institute for Medical Research/Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
Hesketh Geoffrey
Seaman Matthew N J
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Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
1477-9137
Published
2014-05-01
Epub
2014-00-18
Pages
2053-70
Language
English
Region
England
NLM ID
0052457
PMCID
PMC4004978
Subset
IM
Grants
Wellcome Trust · 100140 · United Kingdom
Medical Research Council · G0701444 · United Kingdom
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