Phototransduction in vertebrate rod and cone cells.

Vertebrate photoreceptor cells operate under very dim and bright illumination regimes. A protein machinery in rod and cone cells underlying the light response mediates photoexcitation, the return to the dark state, and adaptation processes. The machinery controls the homeostasis and mutual dependence of two cytoplasmic messengers, cGMP and Ca2+. The signaling pathway starts with light absorption by visual pigments (rhodopsin in rods or cone opsin in cones), which triggers an amplified signaling cascade, leading to the hydrolysis of cGMP and closure of cyclic nucleotide-gated channels in the photoreceptor plasma membrane. Every step in the signaling pathway is turned off by deactivation reactions, and membrane-bound sensory guanylate cyclases catalyze the resynthesis of cGMP under control of a Ca2+-dependent feedback. Inherited retinal diseases cause dysfunction or loss of human vision resulting from mutations that affect the localization or function of photoreceptor-specific proteins. An imbalance of the cGMP/Ca2+ homeostasis is the cellular consequence of several mutations that were identified in proteins controlling cGMP hydrolysis and synthesis.