Sokal I, Li N, Surgucheva I, Warren M J, Payne A M, Bhattacharya S S, Baehr W, Palczewski K
Department of Ophthalmology, School of Medicine, University of Washington, Seattle 98195, USA.
Mol Cell. 1998 Jul;2(1):129-33. doi: 10.1016/s1097-2765(00)80121-5.
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.
当游离钙离子浓度降低时，GCAP1可刺激漂白的脊椎动物光感受器中的光感受器鸟苷酸环化酶（GC），但在暗适应后细胞质中游离钙离子浓度增加时，GCAP1会失活。最近发现GCAP1中的Y99C突变与常染色体显性锥体营养不良有关。我们发现，GCAP1（Y99C）突变体和天然GCAP1在刺激光感受器GC1方面非常有效。然而，突变型GCAP1的钙离子敏感性明显改变，导致在生理黑暗条件下对GC1的刺激减少但持续存在。这些结果与一个模型一致，即在暗适应的视锥细胞中增强的GC活性会导致细胞质中环鸟苷酸（cGMP）水平升高。生理cGMP水平的改变也与其他视网膜变性有关，包括莱伯先天性黑蒙。
