Aquaporin water channels: roles beyond renal water handling

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, H2O2, ions and CO2. 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.