GCAP1 mutations associated with autosomal dominant cone dystrophy.
We discuss the heterogeneity of autosomal dominant cone and cone-rod dystrophies (adCD, and adCORD, respectively). As one of the best characterized adCD genes, we focus on the GUCA1A gene encoding guanylate cyclase activating protein 1 (GCAP1), a protein carrying three high affinity Ca(2+) binding motifs (EF hands). GCAP1 senses changes in cytoplasmic free [Ca(2+)] and communicates these changes to GC1, by either inhibiting it (at high free [Ca(2+)]), or stimulating it (at low free [Ca(2+)]). A number of missense mutations altering the structure and Ca(2+) affinity of EF hands have been discovered. These mutations are associated with a gain of function, producing dominant cone and cone rod dystrophy phenotypes. In this article we review these mutations and describe the consequences of specific mutations on GCAP1 structure and GC stimulation.We discuss the heterogeneity of autosomal dominant cone and cone-rod dystrophies (adCD, and adCORD, respectively). As one of the best characterized adCD genes, we focus on the GUCA1A gene encoding guanylate cyclase activating protein 1 (GCAP1), a protein carrying three high affinity Ca(2+) binding motifs (EF hands). GCAP1 senses changes in cytoplasmic free [Ca(2+)] and communicates these changes to GC1, by either inhibiting it (at high free [Ca(2+)]), or stimulating it (at low free [Ca(2+)]). A number of missense mutations altering the structure and Ca(2+) affinity of EF hands have been discovered. These mutations are associated with a gain of function, producing dominant cone and cone rod dystrophy phenotypes. In this article we review these mutations and describe the consequences of specific mutations on GCAP1 structure and GC stimulation.
Department of Biology, University of Utah, Salt Lake City, UT 84132, USA.
Li
L
Jiang
Wolfgang
W
Baehr
D000595:Amino Acid Sequence; D005799:Genes, Dominant / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006162:Guanylate Cyclase / Q000235:genetics; D051604:Guanylate Cyclase-Activating Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics*
D051604:Guanylate Cyclase-Activating Proteins; D006162:Guanylate Cyclase