Aquaporins (AQP's) are six-pass transmembrane proteins that form channels in membranes. Each monomer contains a central channel formed in part by two asparagine-proline-alanine motifs (NPA boxes) that confer selectivity for water and/or solutes. The monomers assemble into tetramers. Most aquaporins (i.e. AQP0/MIP, AQP1, AQP2, AQP3, AQP4, AQP5, AQP7, AQP8, AQP9, AQP10) passively transport water into and out of cells according to the osmotic gradient across the membrane. Four aquaporins (the aquaglyceroporins AQP3, AQP7, AQP9, AQP10) conduct glycerol, three aquaporins (AQP7, AQP9, AQP10) conduct urea, and one aquaporin (AQP6) conducts anions, especially nitrate. AQP8 also conducts ammonia in addition to water.
AQP11 and AQP12, classified as group III aquaporins, were identified as a result of the genome sequencing project and are characterized by having variations in the first NPA box when compared to more traditional aquaporins. Additionally, a conserved cysteine residue is present about 9 amino acids downstream from the second NPA box and this cysteine is considered indicative of group III aquaporins. Purified AQP11 incorporated into liposomes showed water transport. Knockout mice lacking AQP11 had fatal cyst formation in the proximal tubule of the kidney. Exogenously expressed AQP12 showed intracellular localization. AQP12 is expressed exclusively in pancreatic acinar cells.
Aquaporins are important in fluid and solute transport in various tissues. In adipocytes, glycerol generated by triglyceride hydrolysis is exported by AQP7 and is imported by liver cells via AQP9. AQP1 plays a role in forming cerebrospinal fluid and AQP1, AQP4, and AQP9 appear to be important in maintaining fluid balance in the brain. AQP0, AQP1, AQP3, AQP4, AQP8, AQP9, and AQP11 play roles in the physiology of the hepatobiliary tract. In the kidney, water and solutes are passed out of the bloodstream and into the proximal tubule via the slit-like structure formed by nephrin in the glomerulus. Water is reabsorbed from the filtrate during its transit through the proximal tubule, the descending loop of Henle, the distal convoluted tubule, and the collecting duct. Aquaporin-1 (AQP1) in the proximal tubule and the descending thin limb of Henle is responsible for about 90% of reabsorption (as estimated from mouse knockouts of AQP1). AQP1 is located on both the apical and basolateral surface of epithelial cells and thus transports water through the epithelium and back into the bloodstream. In the collecting duct epithelial cells have AQP2 on their apical surfaces and AQP3 and AQP4 on their basolateral surfaces to transport water across the epithelium. The permeability of the epithelium is regulated by vasopressin, which activates a signaling cascade leading to the phosphorylation of AQP2 and its translocation from intracellular vesicles to the apical membrane of collecting duct cells.
Here, three views of aquaporin-mediated transport have been annotated: a generic view of transport mediated by the various families of aquaporins independent of tissue type, a view of the role of specific aquaporins in maintenance of renal water balance, and a view of the role of specific aquaporins in glycerol transport from adipocytes to the liver.