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PMID: 19922874 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A FAM21-containing WASH complex regulates retromer-dependent sorting.

Developmental cell ·Vol. 17 ·No. 5 ·2009-11-00 ·Pages 699-711

Gomez TS, Billadeau DD

Abstract

The Arp2/3 complex regulates endocytosis, sorting, and trafficking, yet the Arp2/3-stimulating factors orchestrating these distinct events remain ill defined. WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) is an Arp2/3 activator with unknown function that was duplicated during primate evolution. We demonstrate that WASH associates with tubulin and localizes to early endosomal subdomains, which are enriched in Arp2/3, F-actin, and retromer components. Although WASH localized with activated receptors, it was not essential for endocytosis. However, WASH did regulate retromer-mediated retrograde CI-MPR trafficking, which required its association with endosomes, Arp2/3-directed F-actin regulation, and tubulin interaction. Moreover, WASH exists in a multiprotein complex containing FAM21, which links WASH to endosomes and is required for WASH-dependent retromer-mediated sorting. Significantly, without WASH, retromer tubulation was exaggerated, supporting a model wherein WASH links retromer-mediated cargo containing tubules to microtubules for Golgi-directed trafficking and generates F-actin-driven force for tubule scission.

MeSH Terms
Actin-Related Protein 2-3 Complex/metabolism Actins/metabolism Amino Acid Sequence Carrier Proteins/chemistry,genetics,metabolism Cell Line, Tumor Endocytosis Humans Microtubule-Associated Proteins/genetics,metabolism Microtubules/metabolism Molecular Sequence Data Protein Binding Protein Transport Tubulin/metabolism Wiskott-Aldrich Syndrome Protein/genetics,metabolism
Chemicals
Actin-Related Protein 2-3 Complex Actins Carrier Proteins Microtubule-Associated Proteins Tubulin Wiskott-Aldrich Syndrome Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gomez Timothy S
Department of Immunology, Division of Oncology Research and Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. gomez.timothy@mayo.edu
Billadeau Daniel D
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2009.09.009
Email
gomez.timothy@mayo.edu
Published
2009-11-00
Pages
699-711
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2803077
Subset
IM
Grants
NIAID NIH HHS · R01 AI065474 · United States
NIAID NIH HHS · R01 AI065474-05 · United States
NIAID NIH HHS · T32-AI07047 · United States
NIAID NIH HHS · R01-AI065474 · United States
Corrections
CommentIn
PMID: 19922862
External Links
PubMed source DOI: 10.1016/j.devcel.2009.09.009 PMC Full Text View journal details
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