Abstract：
Retinal cyclic nucleotide-gated (CNG) ion channels bind to intracellular cGMP and mediate visual phototransduction in photoreceptor rod and cone cells. Retinal rod CNG channels form hetero-tetramers comprised of three CNGA1 and one CNGB1 protein subunits. Cone CNG channels are similar tetramers consisting of three CNGA3 and one CNGB3 subunits. Calmodulin (CaM) binds to two distinct sites (CaM1: residues 565-587 and CaM2: residues 1120-1147) within the cytosolic domains of rod CNGB1. The binding of Ca2+-bound CaM to CNGB1 promotes the Ca2+-induced desensitization of CNG channels in retinal rods that may be important for photoreceptor light adaptation. Mutations that affect Ca2+-dependent CNG channel function are responsible for inherited forms of blindness. In this review, we propose structural models of the rod CNG channel bound to CaM that suggest how CaM might cause channel desensitization and how dysregulation of the channel may lead to retinal disease.
摘要：
视网膜环核苷酸门控（CNG）离子通道与细胞内cGMP结合，并介导感光杆和视锥细胞的视觉光转导。视网膜杆CNG通道形成由三个CNGA1和一个CNGB1蛋白亚基组成的异源四聚体。锥形CNG通道是由三个CNGA3和一个CNGB3亚基组成的类似四聚体。钙调蛋白(CaM)结合至杆CNGB1的胞浆结构域内的两个不同位点(CaM1:残基565-587和CaM2:残基1120-1147)。Ca2结合的CaM与CNGB1的结合促进了Ca2诱导的视网膜棒中CNG通道的脱敏，这对于光感受器光适应可能很重要。影响Ca2+依赖性CNG通道功能的突变是导致遗传性失明的原因。在这次审查中,我们提出了与CaM结合的杆状CNG通道的结构模型，这些模型表明CaM可能导致通道脱敏，以及通道失调可能导致视网膜疾病。
