Regulation of cGMP synthesis in photoreceptors: role in signal transduction and congenital diseases of the retina.
Calcium feedback in vertebrate photoreceptors regulates synthesis of cGMP, a second messenger in phototransduction. The decrease in the free intracellular Ca(2+) concentrations caused by illumination stimulates two isoforms of retinal membrane guanylyl cyclase (RetGC) via Ca(2+)-sensor proteins and thus contributes to photoreceptor recovery and light adaptation. Unlike other members of the membrane guanylyl cyclase family, retinal guanylyl cyclases do not have identified extracellular peptide ligands. Recoverin-like proteins, GCAP-1 and GCAP-2, interact with the intracellular portion of the cyclases and stimulate its activity through dimerization of the cyclase subunits. Several mutations that affect the function of photoreceptor guanylyl cyclase and the activator protein have been linked to various forms of congenital human retinal diseases, such as Leber congenital amaurosis, cone and cone-rod dystrophy.
Dizhoor
A M
AM
Department of Ophthalmology/Kresge Eye Institute, Wayne State University School of Medicine, K-456, 4717 St. Antoine Boulevard, 48201, Detroit, MI, USA. adizhoor@med.wayne.edu
D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism*; D019281:Dimerization; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D051604:Guanylate Cyclase-Activating Proteins; D006801:Humans; D008027:Light; D008958:Models, Molecular; D010786:Photoreceptor Cells / Q000378:metabolism*; D011956:Receptors, Cell Surface; D012164:Retinal Diseases / Q000151:congenital* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014785:Vision, Ocular
D002135:Calcium-Binding Proteins; C496736:GUCA1A protein, human; C496739:GUCA1B protein, human; D051604:Guanylate Cyclase-Activating Proteins; D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium