Molecular basis of Cadherin Mediated Cell Adhesion

描述（由申请人提供）：钙粘蛋白是最重要和广泛分布的细胞粘附蛋白之一，它们的选择性结合有助于确定脊椎动物和无脊椎动物细胞之间的物理连接。钙粘蛋白的选择性为形成发育中的组织提供了关键的机制。在早期的工作中，我们定义了脊椎动物经典钙粘蛋白粘合相互作用和结形成的原子水平分子机制。在这里，我们提出了三个主要领域的具体目标来建立这项工作：(1)我们将定量确定经典钙粘蛋白之间相互作用的亲和力，并定义这些分子特性的细胞相关性。(2)我们将研究粘附体连接的结构和机制方面；(3)我们将确定果蝇经典钙粘蛋白的结构和结合机制，以便建立一个简单的遗传系统，通过该系统可以测试钙粘蛋白的分子粘附特性对组织发育的影响。

DESCRIPTION (provided by applicant): Cadherins are among the most important and widely distributed cell adhesion proteins, and their selective binding helps to define physical connections between the cells of vertebrates and invertebrates. Cadherin selectivity provides a critical mechanism to shape developing tissues. In earlier work, we defined the atomic-level molecular mechanisms of vertebrate classical cadherin adhesive interaction and junction formation. Here we propose specific aims in three main areas to build on this work: (1) we will quantitatively determine the affinities of interactions among the classical cadherins, and define cellular correlates of these molecular properties. (2) We will investigate structural and mechanistic aspects of adherens junctions, and (3) we will determine structures and binding mechanisms for Drosophila classical cadherins in order to develop a facile genetic system with which the molecular adhesive properties of cadherins can be tested for their effects on tissue development.