title: CULD is required for rhodopsin and TRPL channel endocytic trafficking and survival of photoreceptor cells.
abstract: Endocytosis of G-protein-coupled receptors (GPCRs) and associated channels contributes to desensitization and adaptation of a variety of signaling cascades. In Drosophila melanogaster, the main light-sensing rhodopsin (Rh1; encoded by ninaE) and the downstream ion channel, transient receptor potential like (TRPL), are endocytosed in response to light, but the mechanism is unclear. By using an RNA-Sequencing (RNA-Seq) approach, we discovered a protein we named CULD, a photoreceptor-cell enriched CUB- and LDLa-domain transmembrane protein, that is required for endocytic trafficking of Rh1 and TRPL. CULD localized to endocytic Rh1-positive or TRPL-positive vesicles. Mutations in culd resulted in the accumulation of Rh1 and TRPL within endocytic vesicles, and disrupted the regular turnover of endocytic Rh1 and TRPL. In addition, loss of CULD induced light- and age-dependent retinal degeneration, and reduced levels of Rh1, but not of TRPL, suppressed retinal degeneration in culd-null mutant flies. Our data demonstrate that CULD plays an important role in the endocytic turnover of Rh1 and TRPL, and suggest that CULD-dependent rhodopsin endocytic trafficking is required for maintaining photoreceptor integrity.
authors.affiliation: School of Life Sciences, Beijing Normal University, Beijing, China, 100875 National Institute of Biological Sciences, Beijing, China, 102206.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing, China, 102206 wangtao@nibs.ac.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D054910:Compound Eye, Arthropod / Q000166:cytology / Q000378:metabolism; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster; D004705:Endocytosis; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D021381:Protein Transport; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: C504665:Arr1 protein, Drosophila; D019390:Arrestins; C000611890:CULD protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D050051:Transient Receptor Potential Channels; C074192:trpl protein, Drosophila; D012243:Rhodopsin
keywords: CULD; Endocytosis; Phototransduction; Rhodopsin; TRPL