aquaporins

Aquaporins are a family of integral membrane proteins that form water-selective channels, enabling rapid movement of water across cell membranes. They are essential for cellular and whole-organism water homeostasis and are found across many forms of life. The family was identified in 1992 by Peter Agre, whose discovery of the erythrocyte water channel helped establish aquaporins as a key class of membrane transport proteins.

Most aquaporins assemble as tetramers in the membrane, with each subunit containing a pore that conducts water. Each pore features two conserved NPA motifs (asparagine-proline-alanine) that project into the center of the channel and form a selective constriction together with an aromatic/arginine (ar/R) region. Some family members, known as aquaglyceroporins, also transport glycerol and other small solutes, broadening their functional repertoire beyond pure water transport.

In mammals, multiple aquaporins have distinct tissue distributions and roles. AQP1 is abundant in kidney proximal tubules and microvasculature; AQP2 is expressed in collecting duct cells and is trafficked to the apical membrane in response to vasopressin to increase water reabsorption; AQP4 is prevalent in the brain and contributes to water movement during edema; AQP5 is found in secretory glands such as the salivary and lacrimal glands. Other aquaporins, including AQP3 and AQP7, serve roles in skin, adipose tissue, and other organs.

Regulation includes trafficking to the plasma membrane, phosphorylation, and, in some isoforms, gating that adjusts water permeability in response to physiological cues. Mutations or dysregulation of aquaporins are linked to diseases such as nephrogenic diabetes insipidus, cerebral edema, and glaucoma. Pharmacological inhibitors have been explored as potential therapies, but achieving selective, effective compounds remains challenging. Overall, aquaporins enable regulated water transport necessary for fluid balance and secretion across tissues.