Kefalov Vladimir, Fu Yingbin, Marsh-Armstrong Nicholas, Yau King-Wai
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature. 2003 Oct 2;425(6957):526-31. doi: 10.1038/nature01992.
Retinal rods and cones share a phototransduction pathway involving cyclic GMP. Cones are typically 100 times less photosensitive than rods and their response kinetics are several times faster, but the underlying mechanisms remain largely unknown. Almost all proteins involved in phototransduction have distinct rod and cone variants. Differences in properties between rod and cone pigments have been described, such as a 10-fold shorter lifetime of the meta-II state (active conformation) of cone pigment and its higher rate of spontaneous isomerization, but their contributions to the functional differences between rods and cones remain speculative. We have addressed this question by expressing human or salamander red cone pigment in Xenopus rods, and human rod pigment in Xenopus cones. Here we show that rod and cone pigments when present in the same cell produce light responses with identical amplification and kinetics, thereby ruling out any difference in their signalling properties. However, red cone pigment isomerizes spontaneously 10,000 times more frequently than rod pigment. This high spontaneous activity adapts the native cones even in darkness, making them less sensitive and kinetically faster than rods. Nevertheless, additional factors are probably involved in these differences.
视网膜视杆细胞和视锥细胞共享一条涉及环鸟苷酸的光转导通路。视锥细胞的光敏性通常比视杆细胞低100倍，其反应动力学要快几倍，但潜在机制在很大程度上仍不清楚。几乎所有参与光转导的蛋白质都有不同的视杆细胞和视锥细胞变体。已经描述了视杆细胞和视锥细胞色素之间的性质差异，例如视锥细胞色素的间-II态（活性构象）寿命短10倍，其自发异构化速率更高，但它们对视杆细胞和视锥细胞功能差异的贡献仍属推测。我们通过在非洲爪蟾视杆细胞中表达人类或蝾螈红色视锥细胞色素，以及在非洲爪蟾视锥细胞中表达人类视杆细胞色素来解决这个问题。在这里我们表明，当视杆细胞和视锥细胞色素存在于同一细胞中时，它们产生的光反应具有相同的放大倍数和动力学，从而排除了它们信号特性的任何差异。然而，红色视锥细胞色素的自发异构化频率比视杆细胞色素高10000倍。这种高自发活性即使在黑暗中也能使天然视锥细胞适应，使其比视杆细胞更不敏感且动力学更快。尽管如此，这些差异可能还涉及其他因素。
