{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:04:18Z","timestamp":1780661058986,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,2]]},"group-title":"Cell Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  AP-2 is a key mediator of clathrin-mediated endocytosis (CME) that internalizes cargo from the plasma membrane. NECAP proteins physically bind phosphorylated AP-2 during CME, but their roles during endocytosis remain unresolved, with conflicting reports about their function. Here, we report that\n                  <jats:italic>Drosophila NECAP<\/jats:italic>\n                  is dispensable for development, but antagonizes light-dependent Rhodopsin-1 (Rh1) internalization, a process that occurs through AP-2-mediated endocytosis. Specifically, loss of\n                  <jats:italic>Drosophila NECAP<\/jats:italic>\n                  causes excessive light-dependent Rh1 internalization and an age-related retinal degeneration that can be rescued by photoreceptor-specific expression of a wild-type transgenic\n                  <jats:italic>NECAP.<\/jats:italic>\n                  A\n                  <jats:italic>Drosophila NECAP<\/jats:italic>\n                  mutant transgene, equivalent to a canine\n                  <jats:italic>NECAP1<\/jats:italic>\n                  variant associated with retinal atrophy, failed to rescue the\n                  <jats:italic>NECAP<\/jats:italic>\n                  loss-of-function phenotype in the eye. Furthermore, overexpression of wild-type\n                  <jats:italic>NECAP<\/jats:italic>\n                  suppressed massive Rh1 internalization in a distinct\n                  <jats:italic>Drosophila<\/jats:italic>\n                  model of light-dependent Rh1 endocytosis and retinal degeneration. These results establish NECAP as a negative regulator of light-dependent Rh1 internalization essential for photoreceptor survival.\n                <\/jats:p>","DOI":"10.64898\/2026.06.01.729193","type":"posted-content","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:20:11Z","timestamp":1780413611000},"source":"Crossref","is-referenced-by-count":0,"title":["NECAP antagonizes light-induced Rhodopsin-1 internalization to promote photoreceptor homeostasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-4952","authenticated-orcid":false,"given":"Huai-Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Tyrlik","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030"},{"name":"Genetics & Genomics Graduate Program, Baylor College of Medicine, Houston, TX 77030"},{"name":"Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam I.","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-6759","authenticated-orcid":false,"given":"Ah-Ram","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Perrimon","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-3660","authenticated-orcid":false,"given":"Chen-Yuan","family":"Tseng","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-5989","authenticated-orcid":false,"given":"Hugo J.","family":"Bellen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-535X","authenticated-orcid":false,"given":"Hyung Don","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 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