Signals Regulating Adhesion Dynamics

Adhesions are sites of contact between cells (cell-cell) and between cells and the extracellular matrix (cell-ECM) that are essential for numerous biological processes such as embryogenesis, wound healing, and the immune response. They are composed of many different molecules including adhesion receptors, signaling proteins (e.g., kinases, phos-phatases, and adaptor proteins), and structural proteins (e.g., actin-binding proteins) [1–3]. Adhesions are dynamic structures whose molecular composition and structure can undergo rapid changes to allow cells to respond to external signals [1, 4]. Indeed, this dynamic nature of adhesions within localized regions of cells is critical for many complex processes such as cell migration. For cell-ECM adhesions, their assembly is initiated by the binding of integrin adhesion receptors to the ECM. These new adhesions can either disassemble, allowing cells to migrate, or continue to mature by recruiting signaling and structural proteins to these sites. The dynamics and composition of adhesions are controlled by signaling networks that function to integrate molecular signals from outside and within cells. This special issue focuses on the molecular signals that regulate adhesion dynamics with an emphasis on cell-ECM adhesions. Integrins are transmembrane adhesion receptors that provide a functional link between the ECM and the actin cytoskeleton. Integrin engagement of the ECM serves to transduce signals to the interior of cells which regulate cell behavior. RGD-dependent integrins are a subgroup of adhesion receptors that specifically recognize the RGD motif, which is a three-amino-acid sequence (Arg-Gly-Asp) that is found in some ECM proteins. In this special issue, Y. D. Benoit et al. review recent findings regarding the importance of RGD-dependent integrins in epithelial cell homeostasis. Integrins also play important roles in blood clotting and wound healing by regulating platelet adhesion and aggrega-tion. G. F. Guidetti and M. Torti discuss recent insights into the role of Rap1 in regulating platelet adhesion. Rap1 is a member of the Rap family of small GTPases and is a downstream effector of integrin signaling. A-Kinase-Anchoring Proteins (AKAP) are emerging as pivotal scaffolding proteins that bring together key signaling molecules to modulate cell migration. S. Akakura and I. H. Gelman provide insight into the regulation of AKAP12 and how it contributes to cell adhesion. Moreover, they discuss the scaffolding function of AKAP12 and its contribution to cell migration, maintenance of cytoskeletal architecture, cell proliferation, and cytokine-sis. While integrin-containing matrix contacts were first identified in classic focal adhesions, they have subsequently been shown to exist in other …