Non-conducting functions of ion channels: The case of integrin-ion channel complexes

Started as an academic curiosity more than two decades ago, the idea that ion channels can regulate cellular processes in ways that do not depend on their conducting properties (non-ionic functions) gained traction and is now a flourishing area of research. Channels can regulate physiological processes including actin cytoskeletal remodeling, cell motility, excitation-contraction coupling, non-associative learning and embryogenesis, just to mention some, through non-ionic functions. When defective, non-ionic functions can give rise to channelopathies involved in cancer, neurodegenerative disease and brain trauma. Ion channels exert their non-ionic functions through a variety of mechanisms that range from physical coupling with other proteins, to possessing enzymatic activity, to assembling with signaling molecules. In this article, we take stock of the field and review recent findings. The concept that emerges, is that one of the most common ways through which channels acquire non-ionic attributes, is by assembling with integrins. These integrin-channel complexes exhibit broad genotypic and phenotypic heterogeneity and reveal a pleiotropic nature, as they appear to be capable of influencing both physiological and pathological processes.