Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants.

Published online

Journal Article

Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations-F45L, V209M and F220C-yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

Full Text

Duke Authors

Cited Authors

  • Ploier, B; Caro, LN; Morizumi, T; Pandey, K; Pearring, JN; Goren, MA; Finnemann, SC; Graumann, J; Arshavsky, VY; Dittman, JS; Ernst, OP; Menon, AK

Published Date

  • October 3, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 12832 -

PubMed ID

  • 27694816

Pubmed Central ID

  • 27694816

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms12832

Language

  • eng

Conference Location

  • England