Structural Domains Associated with Permeation, Gating, and Selectivity of Aquaporin Ion Channels Found Across Phyla

Aquaporins AQPs) are an ancient group of channels that arose early in phylogeny and radiated throughout the kingdoms of life. Classified as members of the broad Membrane Intrinsic Protein family, AQPs originally were envisioned as strictly water pores that were constitutively open. International research interest is driving new views of AQPs as multifunctional channels with complex control mechanisms that enable adaptive responses to physiological challenges. An expanding number of AQP classes are being discovered to allow permeation of diverse solutes in parallel to the archetypal substrate water, with channel activities that show subtype-specific regulation by intracellular and extracellular signals. To date, at least 15 classes of AQPs from mammals, plants, insects, and algae have been proposed to carry ions, enabling amino acid sequence comparisons that suggest ion channel functional domains arise from conserved transmembrane, loop, and terminal regions of the tetrameric AQP protein, serving as selectivity filters, gates, and sites for modulation. More AQP ion channel classes likely await discovery pending identification of relevant activators. Subtype-specific control of dual water-and-ion AQP classes orchestrates diverse roles for AQPs across the domains of life, promoting homeostasis, cell motility, nutrient acquisition, redox protection, sensory detection, and intercellular signaling in cells and tissues.