cyclic-gmp and Retinal-Dystrophies

Missense mutations in the GUCA1A gene encoding guanylate cyclase-activating protein 1 (GCAP1) are associated with autosomal dominant cone/cone-rod (CORD) dystrophies. The nature of the inheritance pattern implies that a pool of normal GCAP proteins is present in photoreceptors together with the mutated variant. To assess whether human GCAP1 and GCAP2 may similarly regulate the activity of the retinal membrane guanylate cyclase GC-1 (GC-E) in the presence of the recently discovered E111V-GCAP1 CORD-variant, we combined biochemical and in silico assays. Surprisingly, human GCAP2 does not activate GC1 over the physiological range of Ca

Topics: Algorithms; Animals; Calcium; Cyclic GMP; Guanylate Cyclase; Guanylate Cyclase-Activating Proteins; Humans; Light Signal Transduction; Mice; Models, Theoretical; Mutation; Receptors, Cell Surface; Retinal Dystrophies; Signal Transduction