Molecular aspects of aquaporins.

Water can diffuse freely through the lipid bilayer at a limited rate or by water channel proteins in a rapid speed. Aquaporins (AQPs) are a family of membrane water channel proteins that mainly function as regulators of intracellular and intercellular water flow. They are distributed wildly in specific cell types in multiple organs and tissues. Since the first AQP was identified, 13 AQPs have been characterized in mammals. Structural analysis shows that AQPs are homotetramers with each AQP monomer containing six transmembrane α-helices, two half helices and five connecting loops with two conserved asparagine-proline-alanine (NPA) motifs embedding into the plasma membrane. AQPs are demonstrated to selectively transport water but also some other small molecules. The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions. Aquaporins, in particular, AQP2 plays an important role in some disease conditions such as water loss and gain. Insights into the molecular mechanisms regulating AQPs and its clinical significance are proving to be fundamental for development of novel therapeutic targets or reliable diagnostic and prognostic biomarkers. In this chapter, we summarize the molecular aspects of aquaporins which include the isoforms, crystal structure and the molecular mechanisms underlying the regulation of AQPs, with most focus on arginine vasopressin-regulated AQP2.