In the kidney water and solutes are passed out of the bloodstream and into the proximal tubule via the slit-like structure formed by nephrin in the glomerulus. Water is reabsorbed from the filtrate during its transit through the proximal tubule, the descending loop of Henle, the distal convoluted tubule, and the collecting duct. Aquaporin-1 (AQP1) in the proximal tubule and the descending thin limb of Henle is responsible for about 90% of reabsorption (as estimated from mouse knockouts of AQP1). AQP1 is located on both the apical and basolateral surface of epithelial cells and thus transports water through the epithelium and back into the bloodstream. In the collecting duct epithelial cells have AQP2 on their apical surface and AQP3 and AQP4 on their basolateral surface to transport water across the epithelium. The permeability of the epithelium is regulated by vasopressin, which activates the phosphorylation and subsequent translocation of AQP2 from intracellular vesicles to the plasma membrane.
Walz T, Hirai T, Murata K, Heymann JB, Mitsuoka K, Fujiyoshi Y, Smith BL, Agre P, Engel A.; ''The three-dimensional structure of aquaporin-1.''; PubMedEurope PMCScholia
Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR.; ''Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.''; PubMedEurope PMCScholia
de Mattia F, Savelkoul PJ, Kamsteeg EJ, Konings IB, van der Sluijs P, Mallmann R, Oksche A, Deen PM.; ''Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.''; PubMedEurope PMCScholia
Preston GM, Carroll TP, Guggino WB, Agre P.; ''Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.''; PubMedEurope PMCScholia
Hendriks G, Koudijs M, van Balkom BW, Oorschot V, Klumperman J, Deen PM, van der Sluijs P.; ''Glycosylation is important for cell surface expression of the water channel aquaporin-2 but is not essential for tetramerization in the endoplasmic reticulum.''; PubMedEurope PMCScholia
Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE, Robbins RA, Miercke LJ, Stroud RM.; ''Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance.''; PubMedEurope PMCScholia
Tsunoda SP, Wiesner B, Lorenz D, Rosenthal W, Pohl P.; ''Aquaporin-1, nothing but a water channel.''; PubMedEurope PMCScholia
Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W.; ''Molecular cloning of the receptor for human antidiuretic hormone.''; PubMedEurope PMCScholia
Echeverría V, Hinrichs MV, Torrejón M, Ropero S, Martinez J, Toro MJ, Olate J.; ''Mutagenesis in the switch IV of the helical domain of the human Gsalpha reduces its GDP/GTP exchange rate.''; PubMedEurope PMCScholia
Brito M, Guzmán L, Romo X, Soto X, Hinrichs MV, Olate J.; ''S111N mutation in the helical domain of human Gs(alpha) reduces its GDP/GTP exchange rate.''; PubMedEurope PMCScholia
Takata K, Matsuzaki T, Tajika Y, Ablimit A, Hasegawa T.; ''Localization and trafficking of aquaporin 2 in the kidney.''; PubMedEurope PMCScholia
Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA.; ''Aquaporins in the kidney: from molecules to medicine.''; PubMedEurope PMCScholia
Nielsen S, Smith BL, Christensen EI, Knepper MA, Agre P.; ''CHIP28 water channels are localized in constitutively water-permeable segments of the nephron.''; PubMedEurope PMCScholia
Denker BM, Smith BL, Kuhajda FP, Agre P.; ''Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules.''; PubMedEurope PMCScholia
Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y.; ''Structural determinants of water permeation through aquaporin-1.''; PubMedEurope PMCScholia
Gullingsrud J, Kim C, Taylor SS, McCammon JA.; ''Dynamic binding of PKA regulatory subunit RI alpha.''; PubMedEurope PMCScholia
Katsura T, Gustafson CE, Ausiello DA, Brown D.; ''Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells.''; PubMedEurope PMCScholia
de Groot BL, Engel A, Grubmüller H.; ''A refined structure of human aquaporin-1.''; PubMedEurope PMCScholia
Bedford JJ, Leader JP, Walker RJ.; ''Aquaporin expression in normal human kidney and in renal disease.''; PubMedEurope PMCScholia
Erlenbach I, Wess J.; ''Molecular basis of V2 vasopressin receptor/Gs coupling selectivity.''; PubMedEurope PMCScholia
Burghardt B, Elkaer ML, Kwon TH, Rácz GZ, Varga G, Steward MC, Nielsen S.; ''Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas.''; PubMedEurope PMCScholia
Hub JS, de Groot BL.; ''Mechanism of selectivity in aquaporins and aquaglyceroporins.''; PubMedEurope PMCScholia
Mohr E, Hillers M, Ivell R, Haulica ID, Richter D.; ''Expression of the vasopressin and oxytocin genes in human hypothalami.''; PubMedEurope PMCScholia
Zeidel ML, Ambudkar SV, Smith BL, Agre P.; ''Reconstitution of functional water channels in liposomes containing purified red cell CHIP28 protein.''; PubMedEurope PMCScholia
Kamsteeg EJ, Heijnen I, van Os CH, Deen PM.; ''The subcellular localization of an aquaporin-2 tetramer depends on the stoichiometry of phosphorylated and nonphosphorylated monomers.''; PubMedEurope PMCScholia
Wu B, Steinbronn C, Alsterfjord M, Zeuthen T, Beitz E.; ''Concerted action of two cation filters in the aquaporin water channel.''; PubMedEurope PMCScholia
Beitz E, Wu B, Holm LM, Schultz JE, Zeuthen T.; ''Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons.''; PubMedEurope PMCScholia
Mobasheri A, Marples D.; ''Expression of the AQP-1 water channel in normal human tissues: a semiquantitative study using tissue microarray technology.''; PubMedEurope PMCScholia
Martin BR, Farndale RW, Wong SK.; ''The role of Gs in activation of adenylate cyclase.''; PubMedEurope PMCScholia
Sausville E, Carney D, Battey J.; ''The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line.''; PubMedEurope PMCScholia
Liu J, Wess J.; ''Different single receptor domains determine the distinct G protein coupling profiles of members of the vasopressin receptor family.''; PubMedEurope PMCScholia
Meinild AK, Klaerke DA, Zeuthen T.; ''Bidirectional water fluxes and specificity for small hydrophilic molecules in aquaporins 0-5.''; PubMedEurope PMCScholia
van Balkom BW, Savelkoul PJ, Markovich D, Hofman E, Nielsen S, van der Sluijs P, Deen PM.; ''The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel.''; PubMedEurope PMCScholia
Roudier N, Bailly P, Gane P, Lucien N, Gobin R, Cartron JP, Ripoche P.; ''Erythroid expression and oligomeric state of the AQP3 protein.''; PubMedEurope PMCScholia
Dessauer CW, Chen-Goodspeed M, Chen J.; ''Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.''; PubMedEurope PMCScholia
The four protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The specific isoform activated in response to glucagon signalling is not known. The PKA kinase is a tetramer of two regulatory and two catalytic. The regulatory subunits block the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
The arginine vasopressin (AVP) receptor AVPR2 (Birnbaumer M et al, 1992) is expressed in the kidneys and can bind vasopressin (AVP) (Mohr E et al, 1985; Sausville E et al, 1985). This receptor uses the G protein alpha s subunit as its second messenger system.
The binding of GTP by G(s) alpha causes the heterotrimeric G-protein complex to reorientate, exposing previously bound faces of the G(s) alpha:GTP complex and the G-beta: G-gamma complex. Unlike the case with Gi/o heterotrimers, Gs heterotrimers are not observed to significantly dissociate in living cells.
G(s)-alpha:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it.
Aquaporin-1 (AQP1) passively transports water across the plasma membrane according to the osmotic gradient. In the kidney AQP1 is expressed in endothelial cells of the vasa recta, the proximal tubule, and thin descending limb of Henle, where it functions to recover water from filtrate during urine formation. AQP1 is expressed in many other tissues, such as red blood cells, pancreas, and choroid plexus. AQP1 plays a role in forming cerebrospinal fluid.
Aquaporin-2 (AQP2) passively transports water across membranes according to the osmotic gradient. AQP2 is mainly expressed in principal cells of the collecting duct and connecting tubule in the kidney. AQP2 function is acutely regulated by the antidiuretc hormone vasopressin. In the presence of vasopressin AQP is phosphorylated at Ser256, As inferred from rat and mouse Ser261, Ser264, and Thr269 may also be phosphorylated. These phosphorylations are thought to influence AQP2 trafficking and compartmentalization.
Aquaporin-3 (AQP3) passively transports water and glycerol across the plasma membrane according to the osmotic gradient. AQP3 is expressed in airway epithelia, secretory glands, skin, the collecting ducts of the kidney, and the basolateral surface of intestinal epithelium..
Activated Protein Kinase A phosphorylates Aquaporin-2 at Serine 256. The phosphorylated form of AQP2 then traffics from intracellular vesicles to the apical plasma membrane.
Aquaporin-1 (AQP1) passively transports water across the plasma membrane according to the osmotic gradient. In the kidney AQP1 is expressed in endothelial cells of the vasa recta, the proximal tubule, and thin descending limb of Henle, where it functions to recover water from filtrate during urine formation. AQP1 is expressed in many other tissues, such as red blood cells, pancreas, and choroid plexus. AQP1 plays a role in forming cerebrospinal fluid.
Intracellular vesicles bearing phosphorylated Aquaporin-2 tetramers are transported to the plasma membrane by a mechanism that may involve motor activity of myosin VB (inferred from rat, Nedvetsky et al. 2007) and dynein (inferred from toad bladder, Marples et al. 1996).
Aquaporin-4 (AQP4) passively transports water across the plasma membrane according to the osmotic gradient. AQP4 is expressed in the collecting duct of the kidney and in astroglial cells at the blood-brain barrier and ependymal cells lining the ventricles of the brain.
Aquaporin-1 (AQP1) in the proximal tubule and the descending thin limb of Henle is responsible for about 90% of reabsorption (as estimated from mouse knockouts of AQP1). AQP1 is located on both the apical and basolateral surface of epithelial cells and thus transports water through the epithelium and back into the bloodstream.
In the collecting duct epithelial cells have AQP2 on their apical surface and AQP3 and AQP4 on their basolateral surface to transport water across the epithelium. The permeability of the epithelium is regulated by vasopressin, which activates the phosphorylation and subsequent translocation of AQP2 from intracellular vesicles to the plasma membrane.
Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=432040
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AVP
G-alphaAVP
G-alphaRABFIP2
RAB11AAnnotated Interactions
AVP
G-alphaAVP
G-alphaRABFIP2
RAB11A