Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes.

TitleStructural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes.
Publication TypeJournal Article
Year of Publication2004
AuthorsChuang J-Z, Vega C, Jun W, Sung C-H
JournalJ Clin Invest
Volume114
Issue1
Pagination131-40
Date Published2004 Jul
ISSN0021-9738
KeywordsAmino Acid Substitution, Arrestin, Cell Line, Cells, Cultured, Endocytosis, Humans, Kidney, Mutation, Missense, Phosphorylation, Recombinant Proteins, Retinitis Pigmentosa, Rhodopsin, Transfection
Abstract

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous degenerative eye disease. Mutations at Arg135 of rhodopsin are associated with a severe form of autosomal dominant RP. This report presents evidence that Arg135 mutant rhodopsins (e.g., R135L, R135G, and R135W) are hyperphosphorylated and bind with high affinity to visual arrestin. Mutant rhodopsin recruits the cytosolic arrestin to the plasma membrane, and the rhodopsin-arrestin complex is internalized into the endocytic pathway. Furthermore, the rhodopsin-arrestin complexes alter the morphology of endosomal compartments and severely damage receptor-mediated endocytic functions. The biochemical and cellular defects of Arg135 mutant rhodopsins are distinct from those previously described for class I and class II RP mutations, and, hence, we propose that they be named class III. Impaired endocytic activity may underlie the pathogenesis of RP caused by class III rhodopsin mutations.

DOI10.1172/JCI21136
Alternate JournalJ. Clin. Invest.
PubMed ID15232620
PubMed Central IDPMC437971
Grant ListR01 EY011307 / EY / NEI NIH HHS / United States
EY11307 / EY / NEI NIH HHS / United States