Mechanisms of inactivation in Drosophila phototransduction

光感受器通过将光转换成电信号来响应光。这种“光转导”过程涉及一系列生化步骤，每个步骤都涉及一个或多个特定的蛋白质分子（例如视觉色素和催化酶）。最终的结果是被称为“离子通道”的特殊蛋白质的激活，这些蛋白质嵌入细胞周围的膜中。一旦被激活，离子通道允许带电离子，如钠和钙，进入细胞，从而产生电信号，这些电信号沿着沿着神经传递到大脑。苍蝇的光感受器比脊椎动物眼睛中的同等光感受器能够更快地产生10-100倍的反应，从而代表了动物王国中这种最快的生化信号级联（为什么很难拍苍蝇的主要原因之一！）。光转导可以特别好地研究果蝇有几个原因。首先，我们现在知道了它的整个遗传密码，并且可以操纵它的基因，从而可以改变、删除或将单个基因（以及蛋白质）引入果蝇。其次，我们可以分离苍蝇感光器，并使用一种称为“膜片钳”的技术极其精确地记录它们的电信号。第三，我们的实验室已经开发出专门的和复杂的生理工具，使我们能够监测在活的，响应细胞的光转导的单个分子步骤的速率。为了快速可靠地做出反应，光感受器不仅必须响应光而激活，而且还必须能够在光熄灭时终止其活动。虽然同样重要的感光性能，参与失活的分子步骤知之甚少。在这项研究计划中，我们将联合收割机结合我们的生化和生理方法与遗传操作的不同分子组成的光转导级联提供了一个详细的了解这些失活机制是如何控制和协调，以产生这些光感受器的显着性能。参与产生苍蝇对光反应的分子并不是苍蝇感光器所独有的。即使在人类中，与我们正在研究的分子密切相关的分子也遍布全身。它们在各种各样的过程中发挥重要作用，如各种激素反应，血压调节，味觉和嗅觉，以及疼痛，热和冷的感觉。我们从这些研究中获得的知识不仅会让我们详细了解光感受器是如何看到的，而且由于基本的生化机制被广泛发现，将为身体中许多其他临床重要过程提供新的见解。

Photoreceptors respond to light by converting it into electrical signals. This process of 'phototransduction' involves a cascade of biochemical steps, each of which involves one or more specific protein molecules (e.g. visual pigments and catalytic enzymes). The end result is the activation of specialised proteins known as 'ion channels', embedded in the membrane surrounding the cell. Once activated, ion channels allow charged ions, such as sodium and calcium, into the cell, thereby generating electrical signals that are transmitted along nerves to the brain. Fly photoreceptors are remarkable in being able to generate responses 10-100 x more rapidly than equivalent photoreceptors in vertebrate eyes thereby representing the fastest biochemical signalling cascade of this sort in the animal kingdom (one of the main reasons why it is so hard to swat a fly!). Phototransduction can be particularly well studied in the fruitfly Drosophila for several reasons. Firstly, we now know its entire genetic code, and can manipulate its genes so that individual genes (and hence proteins) can be altered, deleted or introduced into the fly. Secondly, we can isolate fly photoreceptors and record their electrical signals with extreme precision using a technique known as 'patch-clamp'. Thirdly, our laboratory has developed specialized and sophisticated physiological tools that allow us to monitor the rates of individual molecular steps in phototransduction in living, responding cells. In order to respond quickly and reliably photoreceptors must not only activate in response to light, but must also be able to terminate their activity when the light goes off. Although equally important for photoreceptor performance, the molecular steps involved in inactivation are poorly understood. In this research programme we will combine our biochemical and physiological approaches with genetic manipulation of different molecular components of the phototransduction cascade to provide a detailed understanding of how these inactivation mechanisms are controlled and co-ordinated to generate the remarkable performance of these photoreceptors. The molecules involved in generating the fly's response to light are not unique to fly photoreceptors. Even in humans, molecules closely related to those we are studying are found throughout the body. They play important roles in a wide range of processes such as all manner of hormonal responses, regulation of blood pressure, taste and smell, and sensations of pain, hot and cold. The knowledge we gain from these studies will not only give us a detailed understanding of how photoreceptors see but, because the basic underlying biochemical mechanisms are so widely found, will provide new insight into many other, often clinically important processes in the body.