GCAP1(Y99C) MUTANT IS CONSTITUTIVELY ACTIVE IN AUTOSOMAL-DOMINANT CONE DYSTROPHY

Citation
I. Sokal et al., GCAP1(Y99C) MUTANT IS CONSTITUTIVELY ACTIVE IN AUTOSOMAL-DOMINANT CONE DYSTROPHY, MOLECULAR CELL, 2(1), 1998, pp. 129-133
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology",Biology
Journal title
ISSN journal
1097-2765
Volume
2
Issue
1
Year of publication
1998
Pages
129 - 133
Database
ISI
SICI code
1097-2765(1998)2:1<129:GMICAI>2.0.ZU;2-G
Abstract
GCAP1 stimulates photoreceptor guanylate cyclase (GC) in bleached vert ebrate photoreceptors when [Ca2+](free) decreases but is inactivated w hen cytoplasmic [Ca2+](free) increases after dark adaptation. A Y99C m utation in GCAP1 has recently been found to be associated with autosom al dominant cone dystrophy. We show that the GCAP1(Y99C) mutant and na tive GCAP1 are highly effective in stimulation of photoreceptor GC1. T he Ca2+ sensitivity of the mutant GCAP1, however, is markedly altered, causing reduced but persistent stimulation of GC1 under physiological dark conditions. These results are consistent with a model in which e nhanced GC activity in dark-adapted cones leads to elevated levels of cytoplasmic cGMP. Alterations in physiological cGMP levels are also as sociated with other retinal degenerations, including Leber's congenita l amaurosis.