Raftophilic rhodopsin-clusters offer stochastic platforms for G protein signalling in retinal discs

Commun Biol. 2019 Jun 14:2:209. doi: 10.1038/s42003-019-0459-6. eCollection 2019.

Abstract

Rhodopsin is a G protein-coupled receptor (GPCR) that initiates the phototransduction cascade in retinal disc membrane. Recent studies have suggested that rhodopsin forms highly ordered rows of dimers responsible for single-photon detection by rod photoreceptors. Dimerization is also known to confer to rhodopsin a high affinity for ordered lipids (raftophilicity). However, the role of rhodopsin organization and its raftophilicity in phototransduction remains obscure, owing to the lack of direct observation of rhodopsin dynamics and distribution in native discs. Here, we explore the single-molecule and semi-multimolecule behaviour of rhodopsin in native discs. Rhodopsin forms transient meso-scale clusters, even in darkness, which are loosely confined to the disc centre. Cognate G protein transducin co-distributes with rhodopsin, and exhibits lateral translocation to the disc periphery upon activation. We demonstrate that rhodopsin offers inherently distributed and stochastic platforms for G protein signalling by self-organizing raftophilic clusters, which continually repeat generation/extinction in the disc membrane.

Keywords: Computational biophysics; Membrane structure and assembly; Sensory processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Cell Membrane / metabolism
  • Cholesterol / chemistry
  • Computational Biology
  • GTP-Binding Proteins / metabolism*
  • Guanosine Triphosphate / chemistry
  • Light
  • Light Signal Transduction
  • Membrane Microdomains / chemistry*
  • Protein Multimerization
  • Protein Transport
  • Ranidae
  • Receptors, G-Protein-Coupled / metabolism
  • Retina / metabolism*
  • Retinal Rod Photoreceptor Cells / metabolism
  • Rhodopsin / chemistry*
  • Rhodopsin / metabolism
  • Rod Cell Outer Segment / metabolism*
  • Signal Transduction
  • Stochastic Processes

Substances

  • Antibodies
  • Receptors, G-Protein-Coupled
  • Guanosine Triphosphate
  • Rhodopsin
  • Cholesterol
  • GTP-Binding Proteins