Cells are usually surrounded by the extracellular matrix (ECM), and adhesion of the cells to the ECM is a key step in their migration through tissues. Integrins are important receptors for the ECM and form structures called focal adhesions (FAs). Formation and disassembly of FAs are regulated dynamically during cell migration. Adhesion to the ECM has been studied mainly using cells cultured on an ECM-coated substratum, where the rate of cell migration is determined by the turnover of FAs. However, the molecular events underlying the disassembly of FAs are less well understood. We have recently identified both a new regulator of this disassembly process and its interaction partners. Here, we summarize our understanding of FA disassembly by focusing on the proteins implicated in this process. 1. Introduction Adhesion of cells to the ECM is key to the regulation of cellular morphology, migration, proliferation, survival, and differentiation [1, 2]. These functions are indispensable during development and for maintenance of tissue architecture and the induction of tissue repair. Integrins are the predominant receptors that mediate cell adhesion to components of the ECM [3–8]. Integrins are expressed on the cell surface as heterodimers comprised of noncovalently associated α- and β-subunits. Both subunits are type I transmembrane proteins containing both a large extracellular domain responsible for binding to ECM ligands and a cytoplasmic portion (CP) that recruits multiple intracellular proteins. Eighteen different α- and 8 β-subunits have been characterized in mammals, and 24 distinct integrin heterodimers have so far been identified [5, 9, 10]. Each integrin recognizes a distinct ECM ligand. As such, the repertoire of integrins expressed on the surface of a particular cell acts as a sensor of the ECM environment [5]. Attachment of cells to ECM components induces clustering of integrins on the cell surface. The cytoplasmic portions of the clustered integrins then act as a platform for the recruitment of cellular proteins such as adaptor/scaffold and signaling proteins to the inner surface of the plasma membrane, where they form structures called focal adhesions (FAs) (Figure 1) [11–13]. The adaptor/scaffold proteins in FAs, such as talin, paxillin, tensin, p130Cas, and α-actinin, provide strong linkages to the actin cytoskeleton and, thereby, connect cells firmly to the ECM [14–18]. This linkage enables the generation of the tension necessary to alter cell morphology and the traction force necessary to move the cell body during migration. In addition,
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