Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

51Citations
Citations of this article
77Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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.

Cite

CITATION STYLE

APA

Ploier, B., Caro, L. N., Morizumi, T., Pandey, K., Pearring, J. N., Goren, M. A., … Menon, A. K. (2016). Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants. Nature Communications, 7. https://doi.org/10.1038/ncomms12832

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free