The intracellular stimulation of guanylate cyclase (GC) by calcium, a key event in the recovery of the dark state of rod photoreceptors after exposure to light, is mediated by guanylate cyclase-activating proteins (GCAP). GCAPs are calcium-binding proteins belonging to the calmodulin superfamily and are specifically expressed in retina. GCAP3 (Guanylyl cyclase-activating protein 3), also known as GUCA1C (Guanylate cyclase activator 1C), is a 209 amino acid EF-hand calcium binding protein that is activated by the decrease in calcium from the absorption of light by rhodopsin. Activation of GCAP3 leads to stimulation of guanylate cyclase 1 and 2 (GC1 and GC2), which increases cGMP concentration. Calcium sensitive regulation of GC is essential in recovery of the rod receptor dark state following light exposure. There are two isoforms of GCAP3 that are produced as a result of alternative splicing events.
