GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy

Sokal, Izabela and Li, Ning and Surgucheva, Irina and Warren, Martin J. and Payne, Annette and Bhattacharya, Shomi S. and Baehr, Wolfgang and Palczewski, Krzysztof (1998) GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy. Molecular Cell, 2 (1). pp. 129-33. ISSN 1097-2765 . (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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GCAP1 stimulates photoreceptor guanylate cyclase (GC) in bleached vertebrate photoreceptors when [Ca2+]free decreases but is inactivated when cytoplasmic [Ca2+]free increase after dark adaptation. A Y99C mutation in GCAP1 has recently been found to be associated with autosomal dominant cone dystrophy. We show that the GCAP1(Y99C) mutant and native GCAP1 are highly effective in stimulation of photoreceptor GC1. The 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 enhanced GC activity in dark-adapted cones leads to elevated levels of cytoplasmic cGMP. Alterations in physiological cGMP levels are also associated with other retinal degenerations, including Leber's congenital amaurosis.

Item Type: Article
Additional information:
Uncontrolled keywords: Adaptation, Physiological Animals Calcium/pharmacology Calcium-Binding Proteins/chemistry/*genetics/physiology Cattle Cell Line Cloning, Molecular Color Vision Defects/*genetics/metabolism Cones (Retina)/*metabolism Cyclic GMP/metabolism Darkness Enzyme Activation Eye Diseases, Hereditary/*genetics/metabolism Eye Proteins/chemistry/*genetics/physiology Genes, Dominant Guanylate Cyclase/chemistry/metabolism Guanylate Cyclase-Activating Proteins Humans Macular Degeneration Moths Mutagenesis, Site-Directed Optic Atrophies, Hereditary/genetics/metabolism Protein Conformation Recombinant Fusion Proteins/biosynthesis Signal Transduction/genetics/physiology Structure-Activity Relationship
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Martin Warren
Date Deposited: 16 Oct 2009 07:37
Last Modified: 17 Jun 2014 13:19
Resource URI: https://kar.kent.ac.uk/id/eprint/11081 (The current URI for this page, for reference purposes)
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