New insights into the regulation of ion channels by integrins.

By controlling cell adhesion to the extracellular matrix, integrin receptors regulate processes as diverse as cell migration, proliferation, differentiation, apoptosis, and synaptic stability. Because the underlying mechanisms are generally accompanied by changes in transmembrane ion flow, a complex interplay occurs between integrins, ion channels, and other membrane transporters. This reciprocal interaction regulates bidirectional signal transduction across the cell surface and may take place at all levels of control, from transcription to direct conformational coupling. In particular, it is becoming increasingly clear that integrin receptors form macromolecular complexes with ion channels. Besides contributing to the membrane localization of the channel protein, the integrin/channel complex can regulate a variety of downstream signaling pathways, centered on regulatory proteins like tyrosine kinases and small GTPases. In turn, the channel protein usually controls integrin activation and expression. We review some recent advances in the field, with special emphasis on hematology and neuroscience. Some oncological implications are also discussed.