Factors that affect regulation of cGMP synthesis in vertebrate photoreceptors and their genetic link to human retinal degeneration

Cyclic GMP is essential for the ability of rods and cones to respond to the light stimuli. Light triggers hydrolysis of cGMP and stops the influx of sodium and calcium through the cGMP-gated ion channels. The consequence of this event is 2-fold: first, the decrease in the inward sodium current plays...

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular biochemistry 2002-01, Vol.230 (1-2), p.139-147
Main Authors: Olshevskaya, Elena V, Ermilov, Alexandre N, Dizhoor, Alexander M
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Cyclic GMP - biosynthesis
Guanylate Cyclase - genetics
Guanylate Cyclase - metabolism
Guanylate Cyclase-Activating Proteins
Humans
Light
Mutation
Photoreceptor Cells, Vertebrate - enzymology
Photoreceptor Cells, Vertebrate - metabolism
Proteins
Retinal Degeneration - enzymology
Retinal Degeneration - genetics
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cyclic GMP is essential for the ability of rods and cones to respond to the light stimuli. Light triggers hydrolysis of cGMP and stops the influx of sodium and calcium through the cGMP-gated ion channels. The consequence of this event is 2-fold: first, the decrease in the inward sodium current plays the major role in an abrupt hyperpolarization of the cellular membrane; secondly, the decrease in the Ca2+ influx diminishes the free intracellular Ca2+ concentration. While the former constitutes the essence of the phototransduction pathway in rods and cones, the latter gives rise to a potent feedback mechanism that accelerates photoreceptor recovery and adaptation to background light. One of the most important events by which Ca2+ feedback controls recovery and light adaptation is synthesis of cGMP by guanylyl cyclase. Two isozymes of membrane photoreceptor guanylyl cyclase (retGC) have been identified in rods and cones that are regulated by Ca2+-binding proteins, GCAPs. At low intracellular concentrations of Ca2+ typical for light-adapted rods and cones GCAPs activate RetGC, but concentrations above 500 nM typical for dark-adapted photoreceptors turn them into inhibitors of retGC. A variety of mutations found in GCAP and retGC genes have been linked to several forms of human congenital retinal diseases, such as dominant cone degeneration, cone-rod dystrophy and Leber congenital amaurosis.
ISSN:0300-8177
1573-4919
DOI:10.1023/A:1014248208584