Organization and function of the interface between cadherin and the cytoskeleton

钙粘附素是一种多功能的黏附受体，参与动物发育和组织动态平衡。我们特别感兴趣的是钙粘附素在上皮细胞中所起的作用，上皮细胞是动物中发现的主要组织类型。钙粘附素在显著的接触点将细胞连接在一起，称为粘连连接。当钙粘附素功能不正常时，上皮细胞崩溃或形成异常形状，这对动物通常是致命的。钙粘附素只有在与细胞的细胞骨架相连时才能发挥作用。这种连接对于形成和保持附着连接是至关重要的。此外，黏附连接和细胞骨架必须合作来塑造和维持组织。钙粘附素与多种细胞质因子结合，包括α-连环蛋白，这是我们近年来研究的一种蛋白质，它是钙粘蛋白与细胞骨架之间的主要连接物。α-连环蛋白的丢失与钙粘蛋白的丢失会导致相同的缺陷，这一事实突显了钙粘蛋白与细胞角蛋白之间的联系的重要性。然而，钙粘蛋白/α-连环蛋白与肌动蛋白之间的界面非常复杂，因为不仅α-连环蛋白可以与细胞骨架的肌动蛋白细丝结合，而且还有几个结合伙伴可以与肌动蛋白结合。关于这个界面如何调节上皮细胞的发育和稳定性，还有很多需要了解。

Cadherins are multifunctional adhesion receptors involved in animal development and tissue homeostasis. We are particularly interested in the role cadherins play in epithelia, the major tissue type found in animals. Cadherins link cells together at prominent contact points called adherens junctions. When cadherins do not function normally, epithelia collapse or develop abnormal shapes, which is often lethal to the animal. Cadherins can only function when they are linked to the cytoskeleton of a cell. This linkage is crucial to form and maintain adherens junctions. Moreover, adherens junctions and the cytoskeleton have to cooperate to shape and maintain tissues. Cadherins bind to several cytoplasmic factors including α-Catenin, a protein that we have studied in recent years, and that is the major linker between cadherin and the cytoskeleton. The importance of the linkage between cadherin and the cytoskelton is highlighted by the fact that loss of α-Catenin causes the same defects as loss of cadherin. However, the interface between cadherin/α-Catenin and actin is very complex as not only α-Catenin can bind to the actin filaments of the cytoskeleton, but has also several binding partners that can bind to actin. Much remains to be learned about how this interface operates to regulate epithelial development and stability.