GPR179 Membrane Protein Introduction

Introduction of GPR179

GPR179 is encoded by the GPR179 gene. It belongs to the G-protein-coupled receptor (GPCR) family which comprises versatile signaling molecules that mediate the majority of physiological responses to hormones and neurotransmitters. GPR179 belongs to the glutamate receptor or class C GPCR protein, which includes, among others, metabotropic glutamate receptors (GRMs), two γ-aminobutyric acid B receptor (GABABR), the calcium-sensing receptor (CASR), the sweet and umami taste receptors and various orphan receptors.

Function of GPR179 Membrane Protein

It has proved that GPR179 is relevant to the vision of mammalian. GPR179 is required for depolarizing bipolar cell function, and whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary Night Blindness. GPR179 is required for high sensitivity of the metabotropic glutamate receptor 6 (mGluR6) signaling cascade in depolarizing bipolar cells. As we all know, depolarizing photoreceptors and bipolar cells signal via mGluR6, and then photoreceptors constantly release glutamate to adapt to dark. What’s more, GPR179 interacts with TRPM1 and one of its functions is to localize RGS7 and RGS11 near the signaling complex. Another second critical function of GPR179 is to set the state of the TRPM1 channel, allowing it to respond optimally to deactivation of the mGluR6 cascade. In mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression.

Fig.1 3D model of the transmembrane region of GPR179. (Audo, 2012)

Application of GPR179 Membrane Protein in Literature

1. Hasan N., et al. CACNA1S expression in mouse retina: Novel isoforms and antibody cross-reactivity with GPR179. Visual Neuroscience. 2016, 33(33), E009. PubMed ID: 27471951
   
   

   This article performs immunohistochemistry and western blotting to test the expression of GPR179 in HEK293T cells and then indicate that the CACNA1S antibody used here and in the retinal studies published to date, cross-reacts with GPR179.

2. Nishiguchi K.M., et al. Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179. Nature Communications. 2015, 6, 6006. PubMed ID: 25613321
   
   

   This article identifies a mutation in the GPR179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in GPR179 successfully restores the function of both photoreceptors and bipolar cells.

3. Ray T.A., et al. GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells. Journal of Neuroscience. 2014, 34(18), 6334-43. PubMed ID: 24790204
   
   

   Authors in this group 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.

4. Orlandi C., et al. Orphan Receptor GPR179 Forms Macromolecular Complexes with Components of Metabotropic Signaling Cascade in Retina ON-Bipolar Neurons. Investigative Ophthalmology & Visual Science. 2013, 54(10), 7153-7161. PubMed ID: 24114537
   
   

   This article demonstrates that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression.

5. Audo I., et al. Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. American Journal of Human Genetics. 2012, 90(2), 321-330. PubMed ID: 22325361
   
   

   This article performs Whole-exome sequencing to identify mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness.

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Reference

1. Audo I, et al. (2012). Whole-exome sequencing identifies mutations in gpr179 leading to autosomal-recessive complete congenital stationary night blindness. American Journal of Human Genetics. 90(2), 321-330.

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