Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Curr Biol. 2020 Dec 21;30(24):4921-4931.e5. doi: 10.1016/j.cub.2020.09.062. Epub 2020 Oct 15.
Retinal rod and cone photoreceptors mediate vision in dim and bright light, respectively, by transducing absorbed photons into neural electrical signals. Their phototransduction mechanisms are essentially identical. However, one difference is that, whereas a rod visual pigment remains stable in darkness, a cone pigment has some tendency to dissociate spontaneously into apo-opsin and retinal (the chromophore) without isomerization. This cone-pigment property is long known but has mostly been overlooked. Importantly, because apo-opsin has weak constitutive activity, it triggers transduction to produce electrical noise even in darkness. Currently, the precise dark apo-opsin contents across cone subtypes are mostly unknown, as are their dark activities. We report here a study of goldfish red (L), green (M), and blue (S) cones, finding with microspectrophotometry widely different apo-opsin percentages in darkness, being ∼30% in L cones, ∼3% in M cones, and negligible in S cones. L and M cones also had higher dark apo-opsin noise than holo-pigment thermal isomerization activity. As such, given the most likely low signal amplification at the pigment-to-transducin/phosphodiesterase phototransduction step, especially in L cones, apo-opsin noise may not be easily distinguishable from light responses and thus may affect cone vision near threshold.
视网膜中的视杆和视锥细胞分别通过将吸收的光子转化为神经电信号来介导暗中和强光下的视觉。它们的光转导机制基本相同。然而,有一个区别是,虽然视杆视觉色素在黑暗中保持稳定,但视锥色素有一些自发解离为脱辅基视蛋白和视网膜(发色团)而无需异构化的趋势。这种视锥色素的特性早已为人所知,但大多被忽视了。重要的是,由于脱辅基视蛋白具有较弱的组成型活性,即使在黑暗中,它也会触发转导产生电噪声。目前,尚不清楚不同视锥亚型的暗态脱辅基视蛋白含量及其暗态活性。我们在这里报告了对金鱼红(L)、绿(M)和蓝(S)视锥的研究,发现用微分光光度法在黑暗中测得的脱辅基视蛋白百分比差异很大,L 视锥约为 30%,M 视锥约为 3%,S 视锥则可以忽略不计。L 和 M 视锥的暗态脱辅基视蛋白噪声也高于全色素热异构化活性。因此,鉴于在色素到转导蛋白/磷酸二酯酶光转导步骤中信号放大的可能性最小,尤其是在 L 视锥中,脱辅基视蛋白噪声可能不容易与光反应区分开来,因此可能会影响接近阈值的视锥视觉。