Regulation of dynamic cell-cell adhesions by coordinated action of lipid kinases and phosphatases

这项研究项目研究了允许细胞相互附着和识别的分子机制。这种细胞间的黏附是由位于细胞表面的钙粘附素分子家族介导的。钙粘附素允许细胞相互识别，并在识别后相互粘连。通过这种方式，单个细胞的群体可以连接在一起，形成紧密的群体--即身体的组织和器官。钙粘附素黏附的破坏会导致许多重要的疾病，特别是炎症和癌症，这一事实证明了钙粘附素黏附的重要性。因此，了解钙粘附素是如何将细胞结合在一起的，对于我们理解常见疾病的分子基础是必要的。在这个项目中，我们研究钙粘附素是如何发出信号来调节细胞行为的。我们建立在我们最近的发现基础上，E-钙粘素可以激活细胞膜上的一种脂质，PIP3，它被认为是许多细胞活动的关键调节因子。我们的目标是了解这个信号是如何在E-钙粘附素黏附中产生的，以及它是如何引起正常细胞对钙粘附素黏附的反应的。

This research project studies the molecular mechanisms that allow cells to attach to, and recognize, one another. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside on the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, to adhere to each other. By this means, populations of individual cells can be linked together into cohesive populations - i.e. the tissues and organs of the body. The importance of cadherin adhesion is exemplified by the fact that disruption of cadherin adhesion contributes to many important diseases, especially inflammation and cancer. Thus understanding how cadherins hold cells together is necessary for us to understand the molecular basis of common diseases. In this project we study how cadherins signal to regulate cellular behaviour. We build on our recent discovery that E-cadherin can activate a lipid in the cell membrane, PIP3, that is known to be a key regulator of many cellular activities. We aim to understand how this signal is generated in response to E-cadherin adhesion and how it elicits normal cellular responses to cadherin adhesion.