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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1189073","sourcedb":"PMC","sourceid":"1189073","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1189073","text":"Nephrogenic diabetes insipidus (NDI) is a disease characterized by excessive urination and thirst, despite normal production of the antidiuretic hormone arginine vasopressin (AVP) [1]. The inherited forms are either X-linked as a consequence of mutation of the Avpr2 gene [2], or autosomal due to mutation of the Aqp2 gene [3]. Aquaporin-2 (AQP2) is a pore-forming protein belonging to a family of water channels [4], and it is expressed in collecting-duct principal cells in the kidney [5]. Generally these proteins permit the passage of water through the plasma membrane (PM) of cells, several of which carry out this role specifically in the process of water reabsorption from urine in the kidney. It has been established that aquaporins, although functional as a monomer, tetramerize before their insertion into the plasma membrane [4,6]. Furthermore these proteins can also be differentially targeted to distinct regions of the PM; for example, AQP2 is routed to the apical membrane of cells surrounding the collecting duct, whereas other aquaporins (AQP3 or 4) are inserted into the basolateral face. Unlike all other family members, AQP2 is not constitutively inserted into the plasma membrane. Under basal conditions, the protein resides in subapical intracellular vesicles; however, under conditions requiring water retention AQP2 translocates to the apical membrane, permitting water reabsorption [7,8]. For this process to occur, AVP binds its receptor, AVPR2, on the basolateral face of the collecting duct cells, leading to a rise in intracellular cAMP, ultimately resulting in phosphorylation of AQP2 at serine 256 by cAMP-dependent protein kinase [9] and its redistribution to the plasma 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