{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have established that the WASH complex, of which WASHC2C is a key regulatory component, orchestrates endosomal trafficking by activating Arp2/3-mediated actin polymerization. In particular, WASH localizes to early endosomal subdomains rich in Arp2/3, F‑actin, tubulin, and retromer components, where it is not essential for bulk endocytosis but is crucial for retromer‐mediated retrograde transport (e.g., of the CI-MPR). In this setting, WASH promotes the proper scission of membrane tubules by linking retromer-associated cargo tubules to microtubules and by generating localized actin forces."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary work demonstrates that WASH is recruited to these specialized endosomal domains via multivalent interactions mediated by FAM21—a subunit of the WASH regulatory complex—that directly binds the retromer cargo-selective complex (specifically VPS35) using repeated L-F-[D/E] motifs. This multivalency allows FAM21 to “sense” the density of retromer on membranes and, in turn, enables coordinated actin polymerization with retromer sorting and maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInterestingly, while some studies in this collection investigate other facets of cellular trafficking—such as the requirements for vaccinia virus entry via a distinct fluid-phase endocytosis pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and the regulation of mitochondrial dynamics in neurons by an evolutionarily novel armadillo repeat protein family"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "—the core functional insights into WASHC2C emphasize its role in modulating membrane remodeling.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, FAM21, beyond its cytoplasmic role in stabilizing and targeting the WASH complex to endosomes, has been found to shuttle between the cytosol and the nucleus. Within the nucleus it participates in the regulation of NF‑κB-dependent transcription by influencing p65 chromatin binding, thereby extending the functional repertoire of the WASH complex into gene regulatory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Timothy S Gomez, Daniel D Billadeau "}, {"type": "b", "children": [{"type": "t", "text": "A FAM21-containing WASH complex regulates retromer-dependent sorting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2009.09.009"}], "href": "https://doi.org/10.1016/j.devcel.2009.09.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19922874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19922874"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Da Jia, Timothy S Gomez, Daniel D Billadeau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-12-1059"}], "href": "https://doi.org/10.1091/mbc.E11-12-1059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22513087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22513087"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cheng-Yen Huang, Tsai-Yi Lu, Chi-Horng Bair, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel cellular protein, VPEF, facilitates vaccinia virus penetration into HeLa cells through fluid phase endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00894-08"}], "href": "https://doi.org/10.1128/JVI.00894-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18550675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18550675"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Guillermo López-Doménech, Román Serrat, Serena Mirra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms1829"}], "href": "https://doi.org/10.1038/ncomms1829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22569362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22569362"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhi-Hui Deng, Timothy S Gomez, Douglas G Osborne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear FAM21 participates in NF-κB-dependent gene regulation in pancreatic cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.161513"}], "href": "https://doi.org/10.1242/jcs.161513"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25431135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25431135"}]}]}]}