{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GPR179 is an orphan G protein‐coupled receptor that plays a critical role in the organization and function of the ON‐bipolar cell signaling cascade in the mammalian retina. It is predominantly localized at the dendritic tips of ON‐bipolar cells, where it orchestrates metabotropic glutamate receptor 6 (mGluR6)–mediated signaling by recruiting key regulators of G protein signaling—specifically, the RGS proteins RGS7 and RGS11—to the postsynaptic membrane (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " This organized assembly is essential for the precise regulation of the mGluR6 cascade that controls the opening of TRPM1 channels and, consequently, the depolarization of ON‐bipolar cells under light conditions."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Disruption of GPR179 function—by means of missense, splice site, or frameshift mutations—impairs the proper targeting of these signaling components and is linked to autosomal recessive complete congenital stationary night blindness (cCSNB), as demonstrated by the absence of the ERG b‐wave in affected patients and animal models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, studies reveal that GPR179 not only serves as a scaffold for its interacting partners but also undergoes homodimerization via a proximal region in its C‐terminus—possibly through a coiled–coil motif—suggesting that dimer formation may contribute to the stabilization of large postsynaptic signaling complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, identification of aberrant splicing events and deep intronic variants in GPR179 in patients with inherited retinal dystrophies underscores its pathogenic relevance and highlights the need to consider GPR179 mutation status in therapeutic gene replacement strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, by facilitating the precise localization and assembly of the mGluR6 signaling complex and by modulating G protein signaling dynamics, GPR179 is indispensable for proper ON‐bipolar cell function and, consequently, for normal night vision.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabelle Audo, Kinga Bujakowska, Elise Orhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.12.007"}], "href": "https://doi.org/10.1016/j.ajhg.2011.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22325361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22325361"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cesare Orlandi, Ekaterina Posokhova, Ikuo Masuho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201202123"}], "href": "https://doi.org/10.1083/jcb.201202123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22689652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22689652"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Thomas A Ray, Kathryn M Heath, Nazarul Hasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4044-13.2014"}], "href": "https://doi.org/10.1523/JNEUROSCI.4044-13.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24790204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24790204"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cesare Orlandi, Yan Cao, Kirill A Martemyanov "}, {"type": "b", "children": [{"type": "t", "text": "Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.13-12907"}], "href": "https://doi.org/10.1167/iovs.13-12907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24114537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24114537"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christina Zeitz, Samuel G Jacobson, Christian P Hamel, et al. 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