Metabotropic glutamate receptor 6 (mGluR6) (mGluR6)

Metabotropic glutamate receptor 6 (mGluR6), encoded by the GRM6 gene, is the defining molecular target of retinal ON bipolar cells (UniProt Q13589). It is a G protein-coupled receptor (GPCR) located on the post-synaptic dendritic tips of these cells, where it receives glutamatergic input from photoreceptors (PubMed: 8124785). In the dark, continuous glutamate release activates mGluR6, which triggers a G-protein signaling cascade (specifically Gαo) that results in the closure of the TRPM1 cation channel, keeping the cell hyperpolarized (PubMed: 19706471). Upon light exposure, glutamate release decreases, mGluR6 becomes inactive, and TRPM1 channels open, causing the ON bipolar cell to depolarize and transmit the visual signal (StatPearls: Retinal Anatomy). Mutations in mGluR6 are a primary cause of autosomal recessive congenital stationary night blindness (CSNB), characterized by the loss of the ERG b-wave (NIH: GeneReviews). In therapeutic development, mGluR6 and its downstream signaling components are major targets for optogenetic gene therapies designed to restore light sensitivity in patients with advanced retinal degeneration (Nature: Restoring vision with optogenetics).

Other names

GRM6mGlu6Glutamate receptor metabotropic 6GPR158

mGluR6 is a G protein-coupled receptor that mediates the sign-inverting synapse between photoreceptors and ON bipolar cells; glutamate binding activates Gαo, which leads to the closure of TRPM1 cation channels and cell hyperpolarization (PubMed: 8124785, PubMed: 19706471).