Fig. 2: Activation and termination of OPN4 in M1-subtype ipRGCs of mammals.
From: Melanopsin-mediated optical entrainment regulates circadian rhythms in vertebrates
The OPN4-mediated light-sensitive pathways are predominantly triggered by the downstream Gq/11, PLCβ4, and TRPC6/7 cation channels in mammals. Retinaldehyde is covalently bonded to the transmembrane structure in OPN4, and light (especially near 480 nm) can change its conformation from an 11-cis to an all-trans state to a 7-cis state (silent state). It will trigger downstream Gq/11 coupling, causing PLCβ4 to break down PIP2 into DAG and IP3, where DAG activates the opening of the TRPC6/7 cation channels. The activated C-terminus of OPN4 is phosphorylated in response to GRK2/3, resulting in inactivation. This process may also involve β-Arrestin 2. In addition, β-Arrestin 1 leads to the isomer regeneration of OPN4, which serves subsequent light activation. DAG diacylglycerol, Gq/11 G protein subunit alpha q/11, GRK2/3 G protein-coupled receptor kinase 2/3, PLCβ4 phospholipase C-beta 4, PIP2 phosphatidylinositol bisphosphate, IP3 inositol triphosphate, TRPC6/7 transient receptor potential cation channel subfamily C member 6/7.
