Mouse models to study GCAP functions in intact photoreceptors.
In photoreceptor cells cGMP is the second messenger that transduces light into an electrical response. Regulation of cGMP synthesis by Ca2+ is one of the key mechanisms by which Ca2+ exerts negative feedback to the phototransduction cascade in the process of light adaptation. This Ca2+ feedback to retinal guanylyl cyclases (Ret-GCs) is conferred by the guanylate cyclase-activating proteins (GCAPs). Mutations in GCAP1 that disrupt the Ca2+ regulation of Ret-GCs in vitro have been associated with severe human vision disorders. This chapter focuses on recent data obtained from biochemical and electrophysiological studies of GCAP1/GCAP2 knockout mice and other GCAP transgenic mice, addressing: 1. the quantitative aspects of the Ca2+-feedback to Ret-GCs in regulating the light sensitivity and adaptation in intact rods; 2. functional differences between GCAP1 and GCAP2 in intact rod photoreceptors; and 3. whether GCAP mutants with impaired Ca2+ binding lead to retinal disease in vivo by constitutive activation of Ret-GCs and elevation of intracellular cGMP, as predicted from in vitro studies.
Mendez
Ana
A
The Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9112, USA.
Chen
Jeannie
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D051604:Guanylate Cyclase-Activating Proteins; D006801:Humans; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D017785:Photons; D012160:Retina / Q000378:metabolism / Q000502:physiology*; D012164:Retinal Diseases / Q000235:genetics; D013997:Time Factors
D002135:Calcium-Binding Proteins; C496736:GUCA1A protein, human; C496739:GUCA1B protein, human; D051604:Guanylate Cyclase-Activating Proteins; C496737:Guca1a protein, mouse; C496740:Guca1b protein, mouse; D002118:Calcium