GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells

J Neurosci. 2014 Apr 30;34(18):6334-43. doi: 10.1523/JNEUROSCI.4044-13.2014.


Parallel visual pathways are initiated at the first retinal synapse by signaling between the rod and cone photoreceptors and two general classes of bipolar cells. For normal function, ON or depolarizing bipolar cells (DBCs) require the G-protein-coupled receptor, mGluR6, an intact G-protein-coupled cascade and the transient receptor potential melastatin 1 (TRPM1) cation channel. In addition, another seven transmembrane protein, GPR179, is required for DBC function and recruits the regulators of G-protein signaling (RGS) proteins, RGS7 and RGS11, to the dendritic tips of the DBCs. Here we use the Gpr179(nob5) mouse, which lacks GPR179 and has a no b-wave electroretinogram (ERG) phenotype, to demonstrate that despite the absence of both GPR179 and RGS7/RGS11, a small dark-adapted ERG b-wave remains and can be enhanced with long duration flashes. Consistent with the ERG, the mGluR6-mediated gating of TRPM1 can be evoked pharmacologically in Gpr179(nob5) and RGS7(-/-)/RGS11(-/-) rod BCs if strong stimulation conditions are used. In contrast, direct gating of TRPM1 by capsaicin in RGS7(-/-)/RGS11(-/-) and WT rod BCs is similar, but severely compromised in Gpr179(nob5) rod BCs. Noise and standing current analyses indicate that the remaining channels in Gpr179(nob5) and RGS7(-/-)/RGS11(-/-) rod BCs have a very low open probability. We propose that GPR179 along with RGS7 and RGS11 controls the ability of the mGluR6 cascade to gate TRPM1. In addition to its role in localizing RGS7 and RGS11 to the dendritic tips, GPR179 via a direct interaction with the TRPM1 channel alters its ability to be gated directly by capsaicin.

Keywords: GPR179; TRPM1; mGluR6; night blindness; retina; rod bipolar.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Cell Line, Transformed
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Glycine Agents / pharmacology
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proteoglycans / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, GABA-A / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Retina / cytology
  • Retina / metabolism
  • Retinal Bipolar Cells / cytology
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Strychnine / pharmacology
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism


  • Excitatory Amino Acid Antagonists
  • GPR179 protein, mouse
  • Gabrr1 protein, mouse
  • Glycine Agents
  • Nyx protein, rat
  • Proteoglycans
  • Receptors, G-Protein-Coupled
  • Receptors, GABA-A
  • Receptors, Metabotropic Glutamate
  • TRPM Cation Channels
  • Trpm1 protein, mouse
  • cyclopropyl-4-phosphonophenylglycine
  • metabotropic glutamate receptor 6
  • Strychnine
  • Capsaicin
  • Glycine