{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:16:55Z","timestamp":1793157415361,"version":"4.5.0"},"reference-count":43,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and Caenorhabditis elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for noncanonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.<\/jats:p>","DOI":"10.1091\/mbc.e25-11-0547","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:44:10Z","timestamp":1769625850000},"source":"Crossref","is-referenced-by-count":1,"title":["TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1091","volume":"37","author":[{"given":"Yumiko","family":"Oshima","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaminisree","family":"Nagidi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya E.","family":"Moorthy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon","family":"Heier","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A.","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Hardin","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Flajnik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-3843","authenticated-orcid":false,"given":"Bruce E.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016698118"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03796-9"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(76)90222-0"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.01.006"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2021.4102"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202010178"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110189"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.2.1"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-090413-025610"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1080\/01677063.2020.1781851"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.120.303564"},{"key":"B12","doi-asserted-by":"crossref","unstructured":"Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockmanm HA, Borchardt JD, Gehrs KM,\n                      et al.\n                      (2005). A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102, 7227\u201332.","DOI":"10.1073\/pnas.0501536102"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110359"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyae056"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.04.008"},{"key":"B16","first-page":"1","volume":"8","author":"Inglis PN","year":"2007","journal-title":"WormBook"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109557"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00905-5"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1655"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e15-06-0404"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.050"},{"key":"B22","author":"Oshima Y","year":"2025","journal-title":"bioRxiv"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ng1217"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.084"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(86)90314-3"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113844"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ng.976"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.60"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.037408"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1002"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050314"},{"key":"B32","first-page":"110","volume":"21","author":"Smit-McBride Z","year":"2015","journal-title":"Mol Vis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2003.11.025"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.03.013"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1424391112"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.09.001"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441406"},{"key":"B38","first-page":"264","volume":"21","author":"Wang JC","year":"2015","journal-title":"Mol Vis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901600305"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-76550-6_5"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1242\/dev.019547"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1086\/431426"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2022.02.001"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T18:14:40Z","timestamp":1772907280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E25-11-0547"}},"subtitle":[],"editor":[{"given":"John","family":"Wallingford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,1]]}},"alternative-id":["10.1091\/mbc.E25-11-0547"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e25-11-0547","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,1]]},"article-number":"ar24"}}