◾ Regulation of Eukaryotic Aquaporins

Abstract

Membrane-bound water channels known as aquaporins (AQPs) facilitate water transport across biological membranes along osmotic gradients. Since all living cells depend on their ability to maintain water homeostasis, this must be tightly regulated. In eukaryotes, this is achieved by gating, which involves a conformational change of the protein, thereby physically blocking water transport, or by trafficking in which AQPs are shuttled between intracellular storage sites and the plasma membrane. Gating is common amongst plant AQPs in response to environmental stress and has been shown to be triggered by phosphorylation, pH and binding of divalent cations. Gating has been demonstrated for yeast AQPs for which it is believed to confer protection against osmotic shock and rapid freezing. In mammals, AQP regulation is mainly achieved through trafficking. Thirteen AQPs have been identified in humans, the majority of which are regulated by trafficking in response to a wide range of stimuli. The far best characterized trafficking mechanism is that of AQP2 in the kidney collecting duct where it plays a key role in urine concentration. AQP2 trafficking is controlled by the pituitary hormone vasopressin that stimulates phosphorylation of the AQP2 C-terminus, triggering translocation of AQP2 from intracellular storage vesicles to the apical membrane. Defective trafficking of human AQPs can lead to several disease states, for example nephrogenic diabetes insipidus (AQP2) and Sjogren's syndrome (AQP5). In this chapter, we give an overview of what is known about the regulation of eukaryotic AQPs, focusing particularly on structure-function relationships. We discuss the physiological role of AQP regulation, specific regulatory mechanisms and reoccurring themes in both gating and trafficking. (Less)