) Research on cell interactions with extracellular matrix has exploded during the past decade. Fibronectin has been the prototype extracellular matrix molecule for much of this investigation and has been a major focus of this Gordon Conference since 1982. The discovery of integrins in the mid-1980s as receptors for fibronectin and other constituents of the extracellular matrix expanded the scope of the conference. The emerging understanding over the last five years that integrin function and specificity is regulated by plasma membrane and cytosolic molecular partners has further expanded the scope of the conference. Together, fibronectin, integrins, and their binding partners control many basic biological processes including cell adhesion, cell shape, organization of the cytoskeleton and the extracellular matrix, cell motility, regulation of morphogenesis and tissue interactions, immune cell trafficking, regulation of cell activation state and response to growth factors, induction and resolution of inflammation, hemostasis, and wound repair. The following important new insights have developed in the last four years. First, there is a better understanding of the molecular mechanisms involved in regulation of the activation state of integrins, critical to their ability to bind ligand and transduce signals. Second, there is better insight into the nature and regulation of signaling complexes assembled at adhesion sites, including cytoskeletal components, receptor and non-receptor tyrosine kinases, and other elements of signaling cascades. Third, new families of ligands, including TGF- beta, neuronal and immune adhesion molecules, and disintegrins, as well as new families of physically associated molecules including tetraspanins, caveolin, and multiple cytosolic partners have broadened the context within which integrins function. Fourth, by identifying a central role for integrin function and dysfunction in a variety of physiologic and pathologic states, these molecules are now more appropriate for therapeutic use. The conference outlined in this application is directed at communicating these exciting new developments and stimulating discussion among participants from different disciplines. This cross-pollination is a most effective way of stimulating new waves of insight and information.
