{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:11:46Z","timestamp":1789135906873,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,9]]},"group-title":"Cell Biology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH-NEI grant","award":["EY030889"],"award-info":[{"award-number":["EY030889"]}]},{"name":"VitreoRetinal Foundation Grant","award":["2022(R.R.)"],"award-info":[{"award-number":["2022(R.R.)"]}]},{"name":"The University of Minnesota start-up funds","award":["(G.P.L.)."],"award-info":[{"award-number":["(G.P.L.)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Rhodopsin trafficking from the photoreceptor inner segment to the outer segment is essential for photoreceptor function, yet the molecular mechanism(s) regulating this process remain incompletely understood. MYO1C is an actin-based motor protein implicated in intracellular cargo trafficking. Here, we investigated its role in rhodopsin trafficking and photoreceptor cell homeostasis. In-silico docking identified a putative interaction between the MYO1C C-terminal region and the C-terminal region of rhodopsin containing the conserved VxPx ciliary trafficking motif. Biochemical studies confirmed that full-length MYO1C interacts with rhodopsin, whereas deletion of the MYO1C C-terminal domain abolished this interaction. Live-cell imaging, ciliary localization, and fluorescence recovery after photobleaching in hTERT-RPE1 cells demonstrated that the MYO1C C-terminal region is required for efficient rhodopsin trafficking, membrane localization, and ciliary targeting. In native murine rod photoreceptors MYO1C localized to both inner and outer segments. Global\n                  <jats:italic>Myo1c<\/jats:italic>\n                  deficiency in mice caused age-dependent rhodopsin mislocalization, apo-opsin accumulation and progressive retinal dysfunction, characterized primarily by reduced scotopic ERG responses and delayed a-wave recovery, beginning at 6-months, while photopic responses were relatively preserved. Rod-specific\n                  <jats:italic>Myo1c<\/jats:italic>\n                  deletion similarly caused progressive scotopic dysfunction and reduced a-wave recovery following light stimulation. In contrast, cone-specific\n                  <jats:italic>Myo1c<\/jats:italic>\n                  deletion preserved photopic function and a-wave recovery. Together, these findings identify MYO1C as an important regulator of rhodopsin trafficking and demonstrate a preferential, cell-autonomous requirement for MYO1C in maintaining rod photoreceptor homeostasis and phototransduction recovery. These findings establish a mechanistic link between MYO1C-dependent rhodopsin trafficking and age-dependent rod photoreceptor cell dysfunction.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.749496","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:05:17Z","timestamp":1788969917000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights into MYO1C-Mediated Rhodopsin Trafficking and Rod Photoreceptor Homeostasis"],"prefix":"10.64898","author":[{"given":"Rakesh","family":"Radhakrishnan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Roehrich","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebahattin","family":"Cureoglu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altaf A.","family":"Kondkar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 12271, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael da Costa","family":"Monsanto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J van","family":"Kuijk","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn P.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091106550491000_2026.09.04.749496v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.03.002"},{"key":"2026091106550491000_2026.09.04.749496v1.2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-vision-091718-014843","article-title":"Protein Sorting in Healthy and Diseased Photoreceptors","volume":"5","year":"2019","journal-title":"Annu. 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