Summary
Water reabsorption in the kidney represents a critical physiological event in the
maintenance of body water homeostasis. This highly regulated process relies largely
on vasopressin (VP) action and on the VP-sensitive water channel (AQP2) that is expressed
in principal cells of the kidney collecting duct. Defects in the VP signaling pathway
and/or in AQP2 cell surface expression can lead to an inappropriate reduction in renal
water reabsorption and the development of nephrogenic diabetes insipidus, a disease
characterized by polyuria and polydipsia. This review focuses on the major regulatory
steps that are involved in AQP2 trafficking and function. Specifically, we begin with
a discussion on VP-receptor–independent mechanisms of AQP2 trafficking, with special
emphasis on the nitric oxide–cyclic guanosine monophosphate signaling pathway, followed
by a review of the mechanisms that govern AQP2 endocytosis and exocytosis. We then
discuss emerging data illustrating roles played by the actin cytoskeleton on AQP2
trafficking, and lastly we consider elements that affect AQP2 protein expression in
cells. Recent advances in each topic are summarized and are presented in the context
of their potential to serve as a basis for the development of novel therapies that
may ultimately improve life quality of nephrogenic diabetes insipidus patients.
Keywords
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Article info
Footnotes
Supported by National Institutes of Health grant DK38452. Also supported by a Young Investigator Award from the National Kidney Foundation (R.B.), a Swiss Fondation Suisse pour les Bourses en Médicine et Biologie Fellowship and an Executive Committee on Research Fellowship from Massachusetts General Hospital (U.H.), a National Institutes of Health KO8 grant DK075940-01 (H.A.J.L.), and a doctoral level postgraduate scholarship from National Sciences and Engineering Council of Canada (P.N.). The Microscopy Core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43341).
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