Aquaporin water channels: roles beyond renal water handling

• Published in: Nature reviews. Nephrology Vol. 19; no. 9; pp. 604 - 618
• Main Authors: Login, Frédéric H., Nejsum, Lene N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2023; Nature Publishing Group
• Subjects: 631/443; 692/4022; Aquaporins; Medicine; Medicine & Public Health; Nephrology; Physiology; Review Article; Roles
• ISSN: 1759-5061; 1759-507X
• DOI: 10.1038/s41581-023-00734-9

Aquaporin (AQP) water channels are pivotal to renal water handling and therefore in the regulation of body water homeostasis. However, beyond the kidney, AQPs facilitate water reabsorption and secretion in other cells and tissues, including sweat and salivary glands and the gastrointestinal tract. A growing body of evidence has also revealed that AQPs not only facilitate the transport of water but also the transport of several small molecules and gases such as glycerol, H 2 O 2 , ions and CO 2 . Moreover, AQPs are increasingly understood to contribute to various cellular processes, including cellular migration, adhesion and polarity, and to act upstream of several intracellular and intercellular signalling pathways to regulate processes such as cell proliferation, apoptosis and cell invasiveness. Of note, several AQPs are highly expressed in multiple cancers, where their expression can correlate with the spread of cancerous cells to lymph nodes and alter the response of cancers to conventional chemotherapeutics. These data suggest that AQPs have diverse roles in various homeostatic and physiological systems and may be exploited for prognostics and therapeutic interventions. Aquaporins have diverse roles in various homeostatic and physiological systems beyond their role in renal water handling. This Review describes the role of mammalian aquaporins in the transport of solutes other than water and their involvement in processes such as metabolism, cellular migration, cell adhesion, cell polarity and cell signalling. Key points Aquaporin water channels are essential for the regulation of body water homeostasis, especially for renal water handling. Beyond their role in canonical water transport, aquaporins have additional functions and facilitate the transport of multiple other small solutes and gases. Aquaporins are involved in the regulation of cellular migration as well as in epithelial cell–cell adhesion and cellular polarity; the mechanisms that underlie these functions involve water transport-dependent and water transport-independent mechanisms. Aquaporins are also involved in intracellular and intercellular signalling through the regulation of various signalling pathways and via extracellular vesicles. Aquaporins are involved in the development and spread of multiple cancers and may have a role as prognostic markers and/or drug targets; moreover, aquaporins can affect the response of cancer cells to standard anticancer treatments.