Dimerization of visual pigments in vivo

Tao Zhang, Li Hui Cao, Sandeep Kumar, Nduka O. Enemchukwu, Ning Zhang, Alyssia Lambert, Xuchen Zhao, Alex Jones, Shixian Wang, Emily M. Dennis, Amrita Fnu, Sam Ham, Jon Rainier, King-Wai Yau, Yingbin Fu

Research output: Contribution to journalArticle

Abstract

It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin+ Lrat-/- ) expressing, transgenically, short-wavelength-sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor's outer segment. In R-opsin's absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin's presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptidecompetition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling.

Original languageEnglish (US)
Pages (from-to)9093-9098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number32
DOIs
StatePublished - Aug 9 2016

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Keywords

  • Dimerization
  • Protein trafficking
  • Rhodopsin|cone opsin

ASJC Scopus subject areas

  • General

Cite this

Zhang, T., Cao, L. H., Kumar, S., Enemchukwu, N. O., Zhang, N., Lambert, A., Zhao, X., Jones, A., Wang, S., Dennis, E. M., Fnu, A., Ham, S., Rainier, J., Yau, K-W., & Fu, Y. (2016). Dimerization of visual pigments in vivo. Proceedings of the National Academy of Sciences of the United States of America, 113(32), 9093-9098. https://doi.org/10.1073/pnas.1609018113