HIGH-LEVELS OF RHODOPSIN PHOSPHORYLATION IN MISSENSE MUTATIONS OF C-TERMINAL REGION OF RHODOPSIN

Rhodopsin phosphorylation nas investigated using synthetic C-terminal peptides from rhodopsin, The peptides were phosphorylated by expressed rhodopsin kinase (RK) in the presence of a photolyzed truncated rhodo psin at the C-terminus, No peptide phosphorylation was detected under dark or in conditions in which RK was inactive, However, the phosphory lation rate mas significantly higher in the following three peptides: (335M Rho, 330DDEASTTVSKTETSQMAPA; 347S Rho, 330DDEASTTVSKTETSQVASA; a nd 347L Rho: 330DDEASTTVSKTETSQVALA) taken from missense mutations of rhodopsin found in patients,vith autosomal retinitis pigmentosa (ADRP) as compared with that from wild-type rhodopsin (330DDEASTTVSKTETSQVAP A). Distribution of the phosphorylation showed a similar ratio among t hree serines (334, 338 and 353) in 347L Rho mutation to wild type. How ever, 345M Rho and 347S Rho peptides showed higher phosphorylation at Ser(334), The data obtained suggests that an abnormally high rate of p hosphorylation in missense mutations around the rhodopsin C-terminus m ay change the position of phosphorylation and inactivation process of the visual transduction. (C) 1997 Federation of European Biochemical S ocieties.