regulation of water excretion by the kidney represents an essential aspect. Most of the water filtered by the glomeruli is constitutively reabsorbed; a percentage of it is reabsorbed in the renal collecting duct. Avp signaling via receptor type 2 (Avpr2) mediates the process by regulating the translocation of aquaporin channel 2 (Aqp2) from intracellular vesicles to the apical plasma membrane. Avpr2 couples to Gs alpha subunit leading to activation of adenylyl cyclase (ACs), subsequent production of cyclic AMP and triggering of protein kinase A pathway. PKA signaling, a widely used intracellular pathway, is the major route for channeling the cAMP signal. The compartmentalization of PKA signal is regulated by the AKAP family of scaffold proteins (A Kinase Anchoring Protein). AKAPs bring together PKA, the phosphatases and phosphodiesterases (PDE) that modulate the cAMP signal and in certain cases, substrates and AC. Akap7 and members of PDE4 family are associated with Aqp2 bearing vesicles. PKA phosphorylation at serine 256 of human AQP2 is essential for the translocation of the channel. Phosphorylation of transcription factor Creb at serine 133 is necessary for its activation and the subsequent transcription of its many target genes, one of which is Aqp2. PKA also phosphorylates Pde4d, thus regulating its own activity. Cytoskeletal and membrane fusion/docking components involved in the trafficking of Aq2p-bearing vesicles include at a minimum myosin Vb - recruited to vesicles via its receptor Rab11 and the Rab11fip2 mediator, the v-SNARE Vamp2, the t-SNARE Snap23 and syntaxin (3 or 4). In addition, the PDZ domain containing Sipa1 has been identified as a binding partner for Aqp2; its GAP activity towards Rap1 is necessary for the translocation of the channel (Rap1 is involved in actin polymerization). Calcium appears to mediate a cAMP dependent but PKA independent mechanism of Aqp2 translocation. cAMP promotes the transcription of Aqp2; the role of PKA and thus of vasopressin might be by-passed. Withdrawal of Avp signal or hydrolysis of cAMP leads to internalization of Aqp2. Several disorders and syndromes are associated with disturbances in the Aqp2-mediated water transport, in particular congenital Nephrogenic Diabetes Insipidus (NDI), caused by mutations in Avpr2 and more rarely, in Aqp2. To see the ontology report for annotations, GViewer and download click here...(less)