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GCAP1 Mutations Associated with Autosomal Dominant Cone Dystrophy

  • Li Jiang
  • Wolfgang Baehr
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 664)

Abstract

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 Ca2+ binding motifs (EF hands). GCAP1 senses changes in cytoplasmic free [Ca2+] and communicates these changes to GC1, by either inhibiting it (at high free [Ca2+]), or stimulating it (at low free [Ca2+]). A number of missense mutations altering the structure and Ca2+ 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 Ca2+ binding motifs (EF hands). GCAP1 senses changes in cytoplasmic free [Ca2+] and communicates these changes to GC1, by either inhibiting it (at high free [Ca2+]), or stimulating it (at low free [Ca2+]). A number of missense mutations altering the structure and Ca2+ 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.

Keywords

Cone Dystrophy Dominant Cone Slow Retinal Degeneration Putative Effector Protein Autosomal Dominant Cone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of BiologyUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Biology; Department of Ophthalmology, Department of Neurobiology and Anatomy; John A. Moran Eye CenterUniversity of Utah Health Science CenterSalt Lake CityUSA

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