Mechanisms of inactivation in Drosophila phototransduction

光感受器对光的反应是将其转化为电信号。这个“光导”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”的特殊蛋白质被激活，这些蛋白质被嵌入细胞周围的膜中。一旦激活，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，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产生反应的速度快10-100倍，因此代表了动物王国中最快的生化信号级联（这是为什么很难拍苍蝇的主要原因之一！）。由于几个原因，光转导可以在果蝇中得到特别好的研究。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，这样单个基因（以及蛋白质）就可以被改变、删除或引入果蝇。其次，我们可以分离苍蝇的光感受器，并使用一种称为“膜片钳”的技术以极高的精度记录它们的电信号。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，有反应的细胞中光导的单个分子步骤的速率。为了快速而可靠地做出反应，光感受器不仅要对光做出反应，而且要能够在光消失时终止它们的活动。虽然对光感受器的性能同样重要，但人们对失活的分子步骤知之甚少。在这个研究项目中，我们将把我们的生化和生理方法与光传导级联的不同分子成分的遗传操作结合起来，详细了解这些失活机制是如何被控制和协调的，以产生这些光感受器的卓越性能。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。即使在人类身上，与我们正在研究的分子密切相关的分子也遍布全身。它们在许多过程中发挥着重要作用，如各种激素反应、血压调节、味觉和嗅觉、疼痛感觉、冷热感觉。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，而且由于基本的潜在生化机制被广泛发现，将为许多其他的，通常是临床上重要的身体过程提供新的见解。

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.