Molecular basis of Cadherin Mediated Cell Adhesion

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.