Department of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.
Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA.
J Physiol. 2018 Apr 15;596(8):1513-1526. doi: 10.1113/JP275779. Epub 2018 Mar 5.
Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that can modulate the rate of rhodopsin phosphorylation. We describe two additional and perhaps more important functions during photoreceptor light adaptation. Recoverin influences the rate of change of adaptation. In wild-type rods, sensitivity and response integration time adapt with similar time constants of 150-200 ms. In Rv-/- rods lacking recoverin, sensitivity declines faster and integration time is already shorter and not significantly altered. During steady light exposure, rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is deleted, steady-state currents are already larger and rods saturate at brighter intensities. We propose that recoverin modulates spontaneous and light-activated phophodiesterase-6, the phototransduction effector enzyme, to increase sensitivity in dim light but improve responsiveness to change in brighter illumination.
Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that binds to G-protein receptor kinase 1 and can alter the rate of rhodopsin phosphorylation. A change in phosphorylation should change the lifetime of light-activated rhodopsin and the gain of phototransduction, but deletion of recoverin has little effect on the sensitivity of rods either in the dark or in dim-to-moderate background light. We describe two additional functions perhaps of greater physiological significance. (i) When the ambient intensity increases, sensitivity and integration time decrease in wild-type (WT) rods with similar time constants of 150-200 ms. Recoverin is part of the mechanism controlling this process because, in Rv-/- rods lacking recoverin, sensitivity declines more rapidly and integration time is already shorter and not further altered. (ii) During steady light exposure, WT rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is also deleted, steady-state currents are already larger and rods saturate at brighter intensities. We argue that neither (i) nor (ii) can be caused by modulation of rhodopsin phosphorylation but may instead be produced by direct modulation of phophodiesterase-6 (PDE6), the phototransduction effector enzyme. We propose that recoverin in dark-adapted rods keeps the integration time long and the spontaneous PDE6 rate relatively high to improve sensitivity. In background light, the integration time is decreased to facilitate detection of change and motion and the spontaneous PDE6 rate decreases to augment the rod working range.
恢复蛋白是视杆外段的一种小分子、钙结合蛋白，可调节视紫红质磷酸化的速度。在光感受器的光适应过程中，我们描述了另外两个可能更重要的功能。恢复蛋白影响适应的变化速度。在野生型（WT）棒状细胞中，敏感性和响应整合时间以相似的 150-200ms 时间常数适应。在缺乏恢复蛋白的 Rv-/- 棒状细胞中，敏感性下降更快，整合时间已经更短，且没有明显改变。在稳定的光照射下，棒状细胞的循环电流在数十秒的时间内缓慢增加，逐渐扩展棒状细胞的工作范围。在 Rv-/- 棒状细胞中，这种机制被删除，稳态电流已经更大，并且在更亮的强度下棒状细胞饱和。我们提出，恢复蛋白调节自发和光激活的磷酸二酯酶-6（PDE6），即光转导效应酶，以增加在暗光下的敏感性，但改善在更亮的照明下对变化的响应。
恢复蛋白是视杆外段的一种小分子、钙结合蛋白，与 G 蛋白受体激酶 1 结合，可改变视紫红质磷酸化的速度。磷酸化的变化应该改变光激活视紫红质的寿命和光转导的增益，但在黑暗或弱至中等背景光下，缺失恢复蛋白对棒状细胞的敏感性几乎没有影响。我们描述了另外两个可能具有更大生理意义的功能。（i）当环境强度增加时，WT 棒状细胞的敏感性和整合时间以相似的 150-200ms 时间常数下降。恢复蛋白是控制这一过程的机制的一部分，因为在缺乏恢复蛋白的 Rv-/- 棒状细胞中，敏感性下降更快，整合时间已经更短，且不再进一步改变。（ii）在稳定的光照射下，WT 棒状细胞的循环电流在数十秒的时间内缓慢增加，逐渐扩展棒状细胞的工作范围。在 Rv-/- 棒状细胞中，这种机制也被删除，稳态电流已经更大，并且在更亮的强度下棒状细胞饱和。我们认为，无论是（i）还是（ii）都不能由视紫红质磷酸化的调节引起，而可能是由光转导效应酶磷酸二酯酶-6（PDE6）的直接调节引起的。我们提出，在暗适应的棒状细胞中，恢复蛋白保持较长的整合时间和相对较高的自发 PDE6 速率，以提高敏感性。在背景光下，整合时间缩短，以促进对变化和运动的检测，自发 PDE6 速率降低，以增加棒状细胞的工作范围。
