The activity of guanylyl cyclases is regulated by Ca2+-binding, guanylyl cyclase-activating proteins (GCAPs). This regulation is the most important negative feedback mechanism triggered by Ca2+ in light. There are three GCAPs in humans; GUCA1A (Subbaraya et al. 1994), GUCA1B (Surguchov et al. 1997) and GUCA1C (Haeseleer et al. 1999). In darkness, when intracellular Ca2+ is relatively high, GCAPs suppress guanylate cyclase activity. But the light-induced fall in Ca2+ prompts Ca2+ to dissociate from GCAPs and be replaced by Mg2+, allowing the GCAPs to stimulate guanylate cyclase activity by an order of magnitude. Different GCAPs have different affinities for Ca2+. Defects in GCAP1 give rise to cone dystrophy and Lebers congenital amaurosis (https://sph.uth.edu/retnet/).
Knowles, JA, Surguchov, A, Banerjee, P, Subbaraya, I, Baehr, W, Bronson, JD, Ruiz, C, Palczewski, K
Rao, PN, Gorczyca, WA, Subbaraya, I, Pettenati, MJ, Helekar, BS, Zhao, X, Baehr, W, Ruiz, CC, Palczewski, K
Pettenati, M, Li, N, Bronson, D, Wechter, R, Rao, N, Baehr, W, Sokal, I, Haeseleer, F, Palczewski, K
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