Dizhoor A M, Lowe D G, Olshevskaya E V, Laura R P, Hurley J B
Department of Biochemistry, University of Washington, Seattle 98195.
Neuron. 1994 Jun;12(6):1345-52. doi: 10.1016/0896-6273(94)90449-9.
A human photoreceptor membrane guanylyl cyclase, RetGC, was recently cloned and expressed, but its localization and manner of regulation were not defined. We report here that RetGC is detected primarily in outer segments of human photoreceptor cells. Recombinant RetGC can be stimulated by a soluble retinal-specific factor. Ca2+ interferes with stimulation of RetGC by this factor with a cooperativity coefficient of 1.7 and EC50 near 200 nM. The Ca2+ sensitivities of recombinant RetGC and of guanylyl cyclase activity from rod outer segment membranes are very similar. Our findings indicate that RetGC is a photoreceptor-specific guanylyl cyclase which is stimulated by a retinal-specific activator and inhibited by physiologically relevant concentrations of free Ca2+. The Ca2+ sensitivity of RetGC may be responsible for some of the previously reported effects of Ca2+ on light adaptation and recovery of the dark state.
一种人类光感受器膜鸟苷酸环化酶RetGC最近被克隆并表达，但它的定位和调节方式尚未明确。我们在此报告，RetGC主要在人类光感受器细胞的外段被检测到。重组RetGC可被一种可溶性视网膜特异性因子刺激。Ca2+以1.7的协同系数和接近200 nM的EC50干扰该因子对RetGC的刺激。重组RetGC和视杆细胞外段膜鸟苷酸环化酶活性的Ca2+敏感性非常相似。我们的研究结果表明，RetGC是一种光感受器特异性鸟苷酸环化酶，它受到视网膜特异性激活剂的刺激，并被生理相关浓度的游离Ca2+抑制。RetGC的Ca2+敏感性可能是之前报道的Ca2+对光适应和暗态恢复的一些影响的原因。
