Mechanisms of mechanotransduction in primary visceral afferents

机械转导是指机械刺激在感觉神经中转化为信号的过程。这构成了触觉、听觉、位置感和许多内部感知的基础。它也是疼痛的主要组成部分。我们的小组旨在发现哺乳动物机械转导的分子基础，特别是它与消化系统事件信号的关系。我们和我们的合作者是最早探索这个问题的人之一，并发现三个基因负责机械转导的许多方面。每个基因被转录后在感觉神经纤维的膜上产生一个通道或孔，通过允许离子进入并诱导电信号来响应机械力。我们在个体基因破坏的小鼠中的早期发现表明，这些通道之间复杂的积极和消极相互作用必须是正常机械转导的基础。然而，这些通道必须只代表转导机制的一部分，细胞外和细胞内锚不可避免地发挥主要作用。哺乳动物中这种锚定蛋白的身份目前正在出现，我们很幸运能够接触到缺乏特定基因的小鼠，这将提供关于这种作用的候选者的信息。通过我们对消化系统机械传导的研究，以及我们合作者对皮肤机械传导的研究，我们不仅可以确定哺乳动物机械传导的基本机制，还可以揭示肠道特有的机械传导成分。这些特性为机械感觉信号改变本身就是目的的疾病的治疗提供了分子靶点。

Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.