
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.
Molecular Sequence Data, Microtubules, Actin-Related Protein 2-3 Complex, Actins, Endocytosis, Protein Transport, Tubulin, Cell Line, Tumor, Humans, CELLBIO, Amino Acid Sequence, Carrier Proteins, Microtubule-Associated Proteins, Wiskott-Aldrich Syndrome Protein, Developmental Biology, Protein Binding
Molecular Sequence Data, Microtubules, Actin-Related Protein 2-3 Complex, Actins, Endocytosis, Protein Transport, Tubulin, Cell Line, Tumor, Humans, CELLBIO, Amino Acid Sequence, Carrier Proteins, Microtubule-Associated Proteins, Wiskott-Aldrich Syndrome Protein, Developmental Biology, Protein Binding
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