Vasopressin regulates renal water homeostasis via aquaporins (Homo sapiens)
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Description
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. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=432040
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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Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 3',5'-Cyclic AMP | Arrow | REACT_1292 (Reactome)  | ||
| 3',5'-Cyclic AMP | REACT_1532 (Reactome) | |||
| AQP1 tetramer | mim-catalysis | REACT_23786 (Reactome) | ||
| AQP1 tetramer | mim-catalysis | REACT_23841 (Reactome) | ||
| AQP3 tetramer | mim-catalysis | REACT_23789 (Reactome) | ||
| AQP4 tetramer | mim-catalysis | REACT_24005 (Reactome) | ||
| AVPR2
AVP G-alpha | Arrow | REACT_23926 (Reactome) | ||
| AVPR2
AVP G-alpha | REACT_23926 (Reactome) | |||
| AVPR2 | REACT_16964 (Reactome) | |||
| AVP | REACT_16964 (Reactome) | |||
| Adenylate cyclase | REACT_2219 (Reactome) | |||
| G-alpha | REACT_23894 (Reactome) | |||
| G-beta G-gamma | Arrow | REACT_18433 (Reactome) | ||
| G-protein alpha | Arrow | REACT_18433 (Reactome) | ||
| G-protein alpha | REACT_2219 (Reactome) | |||
| GDP | Arrow | REACT_23926 (Reactome) | ||
| GTP | REACT_23926 (Reactome) | |||
| Gs-activated adenylate cyclase | mim-catalysis | REACT_1292 (Reactome) | ||
| MYO5B
RABFIP2 RAB11A | mim-catalysis | REACT_23863 (Reactome) | ||
| PKA catalytic subunit | Arrow | REACT_1532 (Reactome) | ||
| PKA catalytic subunit | mim-catalysis | REACT_23840 (Reactome) | ||
| PKA tetramer | REACT_1532 (Reactome) | |||
| PPi | Arrow | REACT_1292 (Reactome) | ||
| REACT_1292 (Reactome) | Activated adenylate cyclase associated with the plasma membrane catalyzes the reaction of cytosolic ATP to form 3',5'-cyclicAMP and pyrophosphate. | |||
| REACT_1532 (Reactome) | 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. | |||
| REACT_16964 (Reactome) | 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. | |||
| REACT_18433 (Reactome) | 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. | |||
| REACT_2219 (Reactome) | G(s)-alpha:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it. | |||
| REACT_23786 (Reactome) | 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. | |||
| REACT_23788 (Reactome) | 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. | |||
| REACT_23789 (Reactome) | 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.. | |||
| REACT_23840 (Reactome) | 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. | |||
| REACT_23841 (Reactome) | 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. | |||
| REACT_23863 (Reactome) | 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). | |||
| REACT_23894 (Reactome) | The vasopressin receptor type 2 (AVPR2) interacts with G-protein alpha s via the third intracellular loop of AVPR2. | |||
| REACT_23926 (Reactome) | The AVP:AVPR2 complex activates G-protein alpha s by causing a conformational change in G-protein alpha s that causes it to release GDP and bind GTP. | |||
| REACT_24005 (Reactome) | 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. | |||
| Vasopressin receptor type 2 AVP | REACT_23894 (Reactome) | |||
| cAMP PKA regulatory subunit | Arrow | REACT_1532 (Reactome) | ||
| p-S256-AQP2 | mim-catalysis | REACT_23788 (Reactome) |
