Structure and function of focal adhesions

Integrin-dependent cell adhesions come in different shapes and serve in different cell types for tasks ranging from cell-adhesion, migration, and the remodeling of the extracellular matrix to the formation and stabilization of immunological and chemical synapses. A major challenge consists in the identification of adhesion-specific as well as common regulatory mechanisms, motivating the need for a deeper analysis of protein–protein interactions in the context of intact focal adhesions. Specifically, it is critical to understand how small differences in binding of integrins to extracellular ligands and/or cytoplasmic adapter proteins affect the assembly and function of an entire focal adhesion. By using the talin–integrin pair as a starting point, I would like to discuss how specific protein–protein and protein–lipid interactions can control the behavior and function of focal adhesions. By responding to chemical and mechanical cues several allosterically regulated proteins create a dynamic multifunctional protein network that provides both adhesion to the extracellular matrix as well as intracellular signaling in response to mechanical changes in the cellular environment.

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► Mechanisms of integrin activation and induction of the catch bond mechanism.
► Mechanisms of initiation, maturation, sliding and disassembly of focal adhesions.
► How allosteric regulation of integrin and talin control focal adhesion function.
► The role of PIP-lipids in organizing and maintaining the focal adhesion scaffold.
► Focal adhesion function and behavior is linked to specific sets of adapter proteins.