Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Adv Exp Med Biol. 2012;723:769-75. doi: 10.1007/978-1-4614-0631-0_98.
Cone vision mediated by photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Cone CNG channel is composed of two structurally related subunit types, CNGA3 and CNGB3. Naturally occurring mutations in cone CNG channel are associated with a variety of cone diseases including achromatopsia, progressive cone dystrophy, and some maculopathies. Nevertheless, our understanding of the structure of cone CNG channel is quite limited. This is, in part, due to the challenge of studying cones in a rod-dominant mammalian retina. We have demonstrated a robust expression of cone CNG channel and lack of rod CNG channel in the cone-dominant Nrl−/− retina and shown that the Nrl−/− mouse line is a valuable model to study cone CNG channel. This work examined the complex structure of cone CNG channel using infrared fluorescence Western detection combined with chemical cross-linking and blue native-PAGE. Our results suggest that the native cone CNG channel is a heterotetrameric complex likely at a stoichiometry of three CNGA3 and one CNGB3.
视锥细胞光感受器环核苷酸门控（CNG）通道介导的视锥细胞视觉对于中央视觉和色觉以及视力至关重要。视锥细胞 CNG 通道由两种结构上相关的亚基类型组成，即 CNGA3 和 CNGB3。视锥细胞 CNG 通道的自然发生突变与多种视锥细胞疾病有关，包括色盲、进行性视锥细胞营养不良和一些黄斑病变。然而，我们对视锥细胞 CNG 通道的结构的了解相当有限。部分原因是由于在以杆状细胞为主的哺乳动物视网膜中研究视锥细胞存在挑战。我们已经证明了在视锥细胞占主导地位的 Nrl−/−视网膜中，视锥细胞 CNG 通道有强烈的表达，而杆状细胞 CNG 通道则不存在，并且表明 Nrl−/−小鼠系是研究视锥细胞 CNG 通道的一个有价值的模型。本研究使用近红外荧光 Western 检测结合化学交联和蓝色 native-PAGE 来研究视锥细胞 CNG 通道的复杂结构。我们的结果表明，天然的视锥细胞 CNG 通道是一种异四聚体复合物，可能的比例为三个 CNGA3 和一个 CNGB3。
