Photoreceptor membrane guanylate cyclases ( @entity37188 ) are regulated by @entity460 -binding proteins, @entity69743 and @entity69744 . At @entity141 concentrations below 100 nM, characteristic of light-adapted photoreceptors, guanylate cyclase-activating protein (GCAPs) activate @entity37188 , and at free @entity141 concentrations above 500 nM, characteristic of dark-adapted photoreceptors, GCAPs inhibit @entity37188 . A mutation, @entity69745 , in @entity1 @entity69743 was recently found to be linked to @entity6121 in a British family (Payne, A. M., Downes, S. M., Bessant, D. A. R., Taylor, R., Holder, G. E., Warren, M. J., Bird, A. C., and Bhattachraya, S. S. (1998) Hum. Mol. Genet. 7, 273-277). We produced recombinant @entity69745 @entity69743 mutant and tested its ability to activate @entity37188 in vitro at various free @entity141 concentrations. The @entity69745 mutation does not decrease the ability of @entity69743 to activate @entity37188 . However, @entity37188 stimulated by the @entity69745 @entity69743 remains active even at @entity141 concentration above 1 microM. Hence, the cyclase becomes constitutively active within the whole physiologically relevant range of free @entity141 concentrations. We have also found that the @entity69745 @entity69743 can activate @entity37188 even in the presence of @entity141 -loaded nonmutant GCAPs. This is consistent with the fact that cone degeneration was dominant in @entity1 @entity1 who carried such mutation (Payne, A. M., Downes, S. M., Bessant, D. A. R. , Taylor, R., Holder, G. E., Warren, M. J., Bird, A. C., and Bhattachraya, S. S. (1998) Hum. Mol. Genet. 7, 273-277). A similar mutation, @entity69746 , in @entity69744 results in a different phenotype. This mutation apparently does not affect @entity141 sensitivity of @entity69744 . Instead, the @entity69746 @entity69744 stimulates @entity37188 less efficiently than the wild-type @entity69744 . Our data indicate that cone degeneration associated with the @entity69745 mutation in @entity69743 can be a result of constitutive activation of @entity6708 synthesis.

Constitutive activation of photoreceptor guanylate cyclase by @entity69745 mutant of @entity69743 . Possible role in causing XXXX autosomal dominant cone degeneration.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity6708 :: ('CHEBI:16356', 'Chemical') :: ['cGMP'] @entity69743 :: ('2978', 'Gene') :: ['GCAP-1'] @entity69745 :: ('p|SUB|Y|99|C', 'ProteinMutation') :: ['Y99C'] @entity69744 :: ('2979', 'Gene') :: ['GCAP-2'] @entity6121 :: ('MESH:C566719', 'Disease') :: ['autosomal dominant cone dystrophy'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity69746 :: ('p|SUB|Y|104|C', 'ProteinMutation') :: ['Y104C'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity37188 :: ('3000', 'Gene') :: ['RetGC']
@entity1 :: (9606,Species) :: ['human']
