Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa.
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.
Senin
Ivan I
II
Department of Cell Signalling, A. N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russia.
Bosch
Laia
L
Ramon
Eva
E
Zernii
Evgeni Yu
EY
Manyosa
Joan
J
Philippov
Pavel P
PP
Garriga
Pere
P
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
D051603:Recoverin; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1; D015293:Transducin; D002118:Calcium