First Author | Gomez TS | Year | 2009 |
Journal | Dev Cell | Volume | 17 |
Issue | 5 | Pages | 699-711 |
PubMed ID | 19922874 | Mgi Jnum | J:320159 |
Mgi Id | MGI:6869998 | Doi | 10.1016/j.devcel.2009.09.009 |
Citation | Gomez TS, et al. (2009) A FAM21-containing WASH complex regulates retromer-dependent sorting. Dev Cell 17(5):699-711 |
abstractText | 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. |