Cell migration, proliferation, and differentiation are all influenced by cell adhesion to the extracellular matrix (ECM). As cells adhere to the ECM, numerous signals are generated that presumably regulation these aspects of cell behavior by affecting protein-protein interactions and gene expression. For example, cell adhesion is required for myogenesis, but how the ECM generates intracellular signals to affect the determination of myoblasts and their differentiation into skeletal muscle fibers is not well understood. However, zyxin, one of a growing number of proteins that has been localized to sites of cell-ECM adhesion, has recently emerged as a candidate in the regulation of myogenesis because it binds to proteins in the cysteine rich protein (CRP) family that have been shown to potentiate myogenesis. Zyxin associates with members of this protein family through one of its three LIM domains, zinc finger motifs that are also found in transcription factors. In addition to LIM domains, zyxin also contains a proline-rich region that is postulated to associate with SH3 domains of other signalling proteins. In this proposal, biochemical, molecular and cell biological techniques will be utilized to investigate proteins that bind to these domains of zyxin in skeletal muscle and to explore how these interactions may influence the regulation of myogenesis.
