[PDF][PDF] A FAM21-containing WASH complex regulates retromer-dependent sorting

TS Gomez, DD Billadeau - Developmental cell, 2009 - cell.com
TS Gomez, DD Billadeau
Developmental cell, 2009cell.com
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 …
Summary
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.
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