Integrin structure and functional relation with ion channels.

Physical and functional link between cell adhesion molecules and ion channels provide a rapid connection between extracellular environment and cell physiology. Growing evidence does show that frequent cross‑talk occurs between these classes of membrane proteins. These interactions are being addressed in ever increasing molecular detail. Recent advances have given X‑ray resolved structure of the extracellular domains of integrin receptors. Such a level of resolution is still not available for the transmembrane and intracellular domains. Nonetheless, current molecular biological work is unraveling an intricate network connecting the cytoplasmic integrin domains with the cytoskeleton, ion channels and variety of cellular messengers. Overall, these studies show that integrins and ion channels both present bidirectional signaling features. Extracellular signals are usually transduced by integrins to trigger cellular responses that may involve ion fluxes, which can offer further relay. Intracellular processes and ion channel engagement can in turn affect integrin activation and expression and thus cell adhesion to the extracellular matrix. Moreover, ion channels themselves can communicate extracellular messages to both the cytoplasmic environment and integrin themselves. These interactions appear to often depend on formation of multiprotein membrane complexes that can recruit other elements, such as growth factor receptors and cytoplasmic signaling proteins. This chapter provides a general introduction to the field, by giving a brief historical introduction and summarizing the main features of integrin structure and link to the cytoplasmic proteins. In addition, it outlines the main cellular processes in which channel‑integrin interplay is known to exert clear physiological and pathological roles.