Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

Birgit Ploier, Lydia N Caro, Takefumi Morizumi, Kalpana Pandey, Jillian N Pearring, Michael A Goren, Silvia C Finnemann, Johannes Graumann, Vadim Y Arshavsky, Jeremy S Dittman, Oliver P Ernst, Anant K Menon

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number12832
JournalNature Communications
Publication statusPublished - 3 Oct 2016
Externally publishedYes


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