Regulation of Photoreceptor Sensitivity: Biochemical Mechanisms

眼睛的视网膜包含光感受器，在许多生物体中，视网膜对光的敏感度会发生变化。马蹄蟹（limus）是一种多年来一直被用作视觉模型的动物，因为它有特别大的复眼，其大细胞相对容易用于生理和生化研究。在limus中，视网膜的敏感度受到两个因素的调节，光本身会降低敏感度，而从大脑到眼睛的神经，称为传出神经支配，会增加眼睛对光的敏感度。本项目研究了由光和limus光感受器的输出神经支配引发的大部分未知的生化机制，并探讨了它们在细胞内水平上的相互作用。特别是，细胞内钙离子浓度的变化深刻影响光感受器的敏感性。内钙可能通过钙调节酶过程发挥作用，如蛋白激酶活性和蛋白磷酸化。生化工具被用来分离和表征一种有趣的钙活化激酶（称为CaCAM-PK），即使在没有进一步钙升高的情况下，它也可能保持活性。这一特性意味着该激酶可以作为一种分子激活开关。研究的另一种蛋白激酶依赖于钙和磷脂，并作用于光感受器蛋白。这些研究将有助于我们了解光感受器的敏感性是如何被调节的，以及钙是如何影响细胞功能的。

The retina of the eye contains photoreceptors, and in many organisms the sensitivity of the retina to light can change. The horseshoe crab, Limulus, is an animal that has been used for many years as a model for vision because it has particularly large compound eyes, with large cells that are relatively accessible for physiological and biochemical studies. In Limulus, retinal sensitivity is regulated by two factors, light itself, which decreases the sensitivity, and nerves coming from the brain to the eye, called efferent innervation, which increase the sensitivity of the eye to light. This project addresses the largely unknown biochemical mechanisms initiated by light and by efferent innervation in Limulus photoreceptors, and explores their interactions at the intracellular level. In particular, changes produced in intracellular calcium ion concentration profoundly influence photoreceptor sensitivity. Internal calcium may exert its effects by calcium regulation of enzyme processes, such as protein kinase activity and protein phosphorylation. Biochemical tools are used to isolate and characterize one of the interesting calcium-activated kinases (known as CaCAM-PK) that also may remain active even in the absence of further calcium elevation. This property means this kinase can be a kind of molecular activating switch. Another protein kinase studied depends on calcium and phospholipid, and acts on photoreceptor proteins. These studies will contribute significantly to our knowledge of how the sensitivity of photoreceptors is regulated, and also how calcium influences the function of cells in general.