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Moreover, we identify an unexpected role for TFG in the trafficking of Rab4A-positive recycling endosomes specifically within axons and dendrites. Impaired TFG function compromises the transport of at least a subset of endosomal cargoes, which we show results in down-regulated inhibitory receptor signaling that may contribute to excitation-inhibition imbalances. In contrast, the morphology and trafficking of other organelles, including mitochondria and lysosomes, are unaffected by the TFG p.R106C mutation. Our findings demonstrate a multifaceted role for TFG in secretory and endosomal protein sorting that is unique to cells of the central nervous system and highlight the importance of these pathways to maintenance of corticospinal tract motor neurons.<\/jats:p>","DOI":"10.1073\/pnas.2210649119","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T15:21:09Z","timestamp":1664205669000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["TFG regulates secretory and endosomal sorting pathways in neurons to promote their activity and maintenance"],"prefix":"10.1073","volume":"119","author":[{"given":"Jennifer L.","family":"Peotter","sequence":"first","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Pustova","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly M.","family":"Lettman","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Shatadal","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazdak M.","family":"Bradberry","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison D.","family":"Winter-Reed","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-6277","authenticated-orcid":false,"given":"Maya","family":"Charan","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0049-8884","authenticated-orcid":false,"given":"James R.","family":"Alvin","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Bren","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-4167","authenticated-orcid":false,"given":"Annika K.","family":"Oie","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-8140","authenticated-orcid":false,"given":"Edwin R.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705"},{"name":"HHMI, University of Wisconsin-Madison, Madison, WI 53705"},{"name":"Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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