Protein Networks in Integrin-Mediated Adhesions

This chapter appraises the molecular complexity of integrin-mediated adhesions to the extracellular matrix. The network has been presented at several distinct levels, which range from an examination of the entire network, via a survey of specific families of components, to the characterization of functional subnets, then to individual protein entourages and to specific domains of adhesome constituents. These modifications of these domains by signaling molecules have also been discussed. Each of these can act as a "switch" that "turns on" or "turns off" the molecular interactions within the adhesion structure. Current thinking supports the view that adhesion structures serve, not only as means to link cells physically into functional tissues and organs, but also as a means by which cells learn about the nature of their environment. It appears that, via these adhesions, cells sense several features of their neighborhood, including the molecular composition of the matrix, its geometry, and its physical properties. This information is then integrated and translated into specific adhesion-mediated signaling events that drive physiological cellular responses. Most studies of adhesion sites have focused on the in-depth characterization of individual proteins, and the signaling pathways affecting their activity. However, attempts to assign specific biological functions to individual molecules have proven to be difficult, probably because of the enormous complexity of adhesion sites and their diversity. Adhesion sites can be studied in a "bottom-up" approach, "reconstructing" multimolecular function units from their individual constituents, or "top-down," starting with the complex, unperturbed structure.