title: Dimerization of visual pigments in vivo.
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 peptide-competition 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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030;
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030;
authors.forename: Nduka O
authors.initials: NO
authors.lastname: Enemchukwu
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: Alyssia
authors.initials: A
authors.lastname: Lambert
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Alex
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Shixian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Emily M
authors.initials: EM
authors.lastname: Dennis
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030;
authors.forename: Amrita
authors.initials: A
authors.lastname: Fnu
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132;
authors.forename: Sam
authors.initials: S
authors.lastname: Ham
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: Jon
authors.initials: J
authors.lastname: Rainier
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; kyau1@jhmi.edu yingbin.fu@bcm.edu.
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132; Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030; kyau1@jhmi.edu yingbin.fu@bcm.edu.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D051379:Mice; D055355:Opsins / Q000737:chemistry; D055503:Protein Multimerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D012168:Retinal Pigments / Q000737:chemistry* / Q000502:physiology
chemical_list: D055355:Opsins; D017382:Reactive Oxygen Species; D012168:Retinal Pigments
keywords: cone opsin; dimerization; protein trafficking; rhodopsin