mGluR6

Metabotropic glutamate receptor 6 (mGluR6) is a class III G protein-coupled receptor localized at the dendritic tips of retinal ON-bipolar cells, where it mediates glutamate-induced hyperpolarization in response to light increments^[1][2]. Mechanistically, mGluR6 activates the Gα_o protein, which regulates the TRPM1 cation channel, producing the depolarizing b-wave of the electroretinogram essential for the ON visual pathway^[3][4][5]. Proper postsynaptic localization of TRPM1 depends on mGluR6 and its scaffold protein nyctalopin, while trans-synaptic interactions with presynaptic ELFN1 proteins further stabilize the receptor complex^[1][6][7]. In zebrafish, mGluR6 paralogs, mGluR6a and mGluR6b, show differential cone connectivity and spectral responses, highlighting functional divergence across isoforms^[8][9]. Disease relevance is exemplified by congenital stationary night blindness, where mutations in either TRPM1 or mGluR6 impair ON-bipolar cell signaling without gross retinal morphology changes^[3][10]. In experimental models, optogenetic fusion of melanopsin to mGluR6 intracellular domains (Opto-mGluR6) restores light responses in degenerated retinas, demonstrating its utility for vision restoration studies^[11]. Pharmacologically, selective mGluR6 agonists such as L-AP4 enhance TRPM1-mediated Ca²⁺ influx in melanocytes, whereas inhibitors like voriconazole block ON-bipolar cell responses by targeting TRPM1 downstream of mGluR6^[5][12]. Compared with related group III mGluRs, mGluR6 uniquely mediates direct photoreceptor-to-ON-bipolar cell transmission, a critical feature distinguishing it from mGluR7 and mGluR8^[13][7].