Research on cell interactions with extracellular matrices 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 on this Gordon Conference since 1982. The discovery of integrins in the mid-1980s as receptors for fibronectin and other constituents of extracellular matrices expanded the scope of the conference. The emerging understanding over the last five years that plasma membrane and cytosolic molecular partners regulate integrin function and specificity 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. Important new insights have been made in recent years, including: ? ? Determination of the first crystal structure of the extracellular domain of an integrin. This work provides a platform for detail molecular dissection of integrin function. ? ? Molecular mechanisms involved in regulation of the activation state of integrins, critical to their ability to bind ligand and transduce signals. ? ? 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. ? New families of ligands including growth factors, neuronal and immune adhesion molecules, and disintegrins, and new families of physically-associated molecules including growth factor and other receptors, tetraspanins, caveolin, and multiple cytosolic partners, that have broadened the context within which integrins function. ? ? A central role for integrin function and dysfunction in a variety of physiologic and pathologic states, which make these molecules focused therapeutic targets. ? ? 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. ? ?
