title: Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa.
abstract: No single molecular mechanism accounts for the effect of mutations in rhodopsin associated with retinitis pigmentosa. Here we report on the specific effect of a Ca2+/recoverin upon phosphorylation of the autosomal dominant retinitis pigmentosa R135L rhodopsin mutant. This mutant shows specific features like impaired G-protein signaling but enhanced phosphorylation in the shut-off process. We now report that R135L hyperphosphorylation by rhodopsin kinase is less efficiently inhibited by Ca2+/recoverin than wild-type rhodopsin. This suggests an involvement of Ca2+/recoverin into the molecular pathogenic effect of the mutation in retinitis pigmentosa which is the cause of rod photoreceptor cell degeneration. This new proposed role of Ca2+/recoverin may be one of the specific features of the proposed new Type III class or rhodopsin mutations associated with retinitis pigmentosa.
authors.affiliation: Department of Cell Signalling, A. N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russia.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Senin
authors.forename: Laia
authors.initials: L
authors.lastname: Bosch
authors.forename: Eva
authors.initials: E
authors.lastname: Ramon
authors.forename: Evgeni Yu
authors.initials: EY
authors.lastname: Zernii
authors.forename: Joan
authors.initials: J
authors.lastname: Manyosa
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Philippov
authors.forename: Pere
authors.initials: P
authors.lastname: Garriga
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D005799:Genes, Dominant; D009154:Mutation; D010766:Phosphorylation; D051603:Recoverin / Q000737:chemistry* / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics*; D015293:Transducin / Q000378:metabolism
chemical_list: D051603:Recoverin; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1; D015293:Transducin; D002118:Calcium