Guanylate cyclase-activating proteins

A second class of neuronal calcium sensors is formed by the guanylate cyclase-activating protein (GCAP). The GCAPs are expressed only in the photoreceptor cells of the retina of vertebrates. Recoverins and GCAPs have antagonistic roles in phototransduction. 

GUANYLATE CYCLASE-ACTIVATING PROTEINS AND RETINA DISEASE... 

Downes, S.M., Holder, G.E., Fitzke, F.W., Payne, A.M., Warren, M.J., Bhattacharya, S.S., and Bird, A.C. (2001a). Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1. Arch. Ophthalmol. 119 96-105. 

Mendez, A., Burns, M.E., Sokal, I., Dizhoor, A.M., Baehr, W., Palczewski, K., Baylor, D.A., and Chen, J. (2001). Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proc. Natl. Acad. Sci. U. S. A 98 9948-9953. 

Michaelides, M., Wilkie, S.E., Jenkins, S., Holder, G.E., Hunt, D.M., Moore, A.T., and Webster, A.R. (2005). Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy. Ophthalmology 112 1442-1447. 

Nishiguchi, K.M., Sokal, I., Yang, L., Roychowdhury, N., Palczewski, K., Berson, E.L., Dryja, T.P., and Baehr, W. (2004). A Novel Mutation (1143NT) in Guanylate Cyclase-Activating Protein 1 (GCAP1) Associated with Autosomal Dominant Cone Degeneration. Invest Ophthalmol. Vis. Sci 45 3863-3870. 

Otto-Bruc, A., Buczylko, J., Surgucheva, I., Subbaraya, I., Rudnicka-Nawrot, M., Crabb, J., Arendt, A., Hargrave, P.A., Baehr, W., and Palczewski, K. (1997a). Functional reconstitution of photoreceptor guanylate cyclase with native and mutant forms of guanylate cyclase activating protein 1. Biochemistry 36 4295 1302. 

Yamazaki, A., Yamazaki, M., Yamazaki, R.K., and Usukura, J. (2006). Illuminated rhodopsin is required for strong activation of retinal guanylate cyclase by guanylate cyclase-activating proteins. Biochemistry 45 1899-1909. 

The ANP leceptoi exists in two forms, ANP and ANPg, both of which have been cloned. These membrane-bound guanylate cyclases have a single transmembrane domain, an intracellular protein kinase-like domain, and a catalytic cyclase domain, activation of which results in the accumulation of cychc guanosine monophosphate (cGMP). A third receptor subtype (ANP ) has been identified that does not have intrinsic guanylate cyclase activity and may play a role in the clearance of ANP. 

The ANP receptor has intrinsic guanylate cyclase activity. Because no G protein is required in the membrane, the receptor Jacks the 7-helix membrane-spanning domain. 

The on signal for guanylate cyclase activation by NO is represented by the binding of NO to heme and the accompanying detachment of the heme Fe axial ligand from the enzyme protein. The off signal is represented by breakdown of the unstable NO-heme complex with liberation of NO and reestablishment of the heme Fe axial ligand. 

Kojda, G., Laursen, J.B., Ramasamy, S., Kent, J.D., Kurz, S., Burchfield, J., Shesely, E.G., Harrison, D.G. Protein expression, vascular reactivity and soluble guanylate cyclase activity in mice lacking the endothelial cell nitric oxide synthase contributions of NOS isoforms to blood pressure and heart rate control, Cardiovasc. Res. 1999, 42, 206-213. 

Mittal, C. K., Arnold, W. P., and Murad, F. (1978). Characterization of protein inhibitors of guanylate cyclase activation from rat heart and bovine lung. J. Biot. Chem. 253, 1266-1271. 

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