| Rhodopsin, also called visual purple, is a prototypical G‑protein‑coupled receptor of the seven‑transmembrane helix family that serves as the primary photopigment in rod photoreceptors and initiates the phototransduction cascade responsible for scotopic vision. The protein consists of an opsin apoprotein embedded in the disk membranes of the rod outer segment, covalently linked via a Schiff base to the 11‑cis retinal chromophore, and carries characteristic GPCR structural elements such as a conserved disulfide bond, N‑terminal glycosylation sites, and palmitoylated cysteines in the C‑terminal tail that stabilize its conformation and membrane localization. Absorption of a photon induces isomerization of 11‑cis retinal to all‑trans retinal and drives rhodopsin from its inactive ground state through a series of intermediates to the active Meta II form, which adopts a conformation that enables high‑affinity coupling to the heterotrimeric G protein transducin and catalyzes exchange of GDP for GTP on the transducin α‑subunit. Activated transducin stimulates cGMP phosphodiesterase, leading to a drop in cytoplasmic cGMP and closure of cGMP‑gated cation channels, which results in hyperpolarization of the rod plasma membrane and generation of the electrical signal that is transmitted to downstream retinal neurons. Termination and resetting of this signaling cycle rely on phosphorylation of the rhodopsin C‑terminal tail by rhodopsin kinase followed by arrestin binding, which blocks further transducin activation, while the all‑trans retinal is released and converted back to 11‑cis retinal through the retinoid cycle before reattachment to opsin. The arrangement of transmembrane helices, the retinal binding pocket, and cytoplasmic loops enables specific amino acid substitutions to alter receptor stability, retinal interaction, and G‑protein coupling, which provides a basis for diverse disease‑associated variants. Mutations in the rhodopsin gene account for a substantial fraction of autosomal dominant retinitis pigmentosa, and different mutant classes can cause degeneration through protein misfolding and aggregation, mislocalization away from the outer segment disks, production of toxic by‑products during abnormal chromophore handling, or aberrant signaling activity that disturbs photoreceptor homeostasis. Other rhodopsin mutations cluster near the retinal attachment site and produce constitutive activity without major structural degeneration, a pattern linked to congenital stationary night blindness, where rod signaling is chronically desensitized, but photoreceptors remain largely intact. |
