Caring about the other 47% of the water channels. Focus on “Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel”

IT IS SAID THAT WHEN AN EXPERIMENT gives an expected result, nothing is really learned; rather, it is more often from the experiment that gives an unexpected result that something new is learned. In work reported in this issue, Yui and colleagues decided to care about, rather than ignore, their unexpected observations (14). The water channel aquaporin-2 (AQP2) has been a seminal member of the family of membrane channels and transporters whose activity depends on regulated recycling from an intracellular membrane storage compartment to the plasma membrane, typically in a hormone-, secretagogue-, or neurotransmitter-dependent fashion (4). It is widely accepted that the mechanism of regulated water reabsorption from the lumen of the distal tubule and collecting duct of the nephron is due to the vasopressin-dependent recycling of AQP2 at the apical membrane of these epithelial cells (9). In addition, until now, it was thought to be equally likely that, once AQP2 left the biosynthetic pathway, it was targeted directly to the subapical membrane compartment or to the apical membrane. However, despite the predominant steadystate (sub)apical localization of AQP2 observed in an overwhelming number of in vivo and cell culture systems, Yui and colleagues provide experimental evidence, cobbled together with other data in the literature, for a more complex picture of AQP2 trafficking in polarized epithelial cells, one which surprisingly may include its targeting to the basolateral membrane and subsequent transcytosis to the apical membrane (Fig. 1). In AQP2-transfected Madin-Darby canine kidney (MDCK) cells, Yui and colleagues describe conditions in cell-surface biotinylation and immunofluorescence experiments in which Address for reprint requests and other correspondence: C. T. Okamoto, Dept. of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Univ. of Southern California, Los Angeles, CA 90089-9121 (e-mail: cokamoto @usc.edu).