aquaporin 2


Summary: Aquaporin 2 is a water-specific channel protein that is expressed in KIDNEY COLLECTING DUCTS. The translocation of aquaporin 2 to the apical PLASMA MEMBRANE is regulated by VASOPRESSIN, and MUTATIONS in AQP2 have been implicated in a variety of kidney disorders including DIABETES INSIPIDUS.

Top Publications

  1. Procino G, Caces D, Valenti G, Pessin J. Adipocytes support cAMP-dependent translocation of aquaporin-2 from intracellular sites distinct from the insulin-responsive GLUT4 storage compartment. Am J Physiol Renal Physiol. 2006;290:F985-94 pubmed
    ..Together, these data demonstrate that adipocytes display two different intracellular sorting mechanisms that direct distinct hormone-sensitive partitioning of GLUT4 and AQP2. ..
  2. Matthesen S, Larsen T, Vase H, Lauridsen T, Jensen J, Pedersen E. Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial. Clin Exp Hypertens. 2013;35:313-24 pubmed publisher
    ..Amiloride is less effective than spironolactone to reduce renal potassium excretion. ..
  3. Moeller H, Praetorius J, Rützler M, Fenton R. Phosphorylation of aquaporin-2 regulates its endocytosis and protein-protein interactions. Proc Natl Acad Sci U S A. 2010;107:424-9 pubmed publisher
  4. Tamma G, Robben J, Trimpert C, Boone M, Deen P. Regulation of AQP2 localization by S256 and S261 phosphorylation and ubiquitination. Am J Physiol Cell Physiol. 2011;300:C636-46 pubmed publisher
    ..These data indicate that the membrane localization of AQP2 is determined by the balance of the extents of phosphorylation and ubiquitination...
  5. Gooch J, Guler R, Barnes J, Toro J. Loss of calcineurin Aalpha results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus. J Cell Sci. 2006;119:2468-76 pubmed
    ..One potential target of calcineurin action is the water channel aquaporin 2 (AQP2). In this study, we examined the effect of loss of calcineurin Aalpha (CnAalpha) on AQP2 function in vivo...
  6. Nielsen J, Hoffert J, Knepper M, Agre P, Nielsen S, Fenton R. Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: mechanisms for aquaporin 2 down-regulation and cellular proliferation. Proc Natl Acad Sci U S A. 2008;105:3634-9 pubmed publisher
    ..chronic treatment with lithium induces numerous kidney-related side effects, such as dramatically reduced aquaporin 2 (AQP2) abundance, altered renal function, and structural changes...
  7. Loonen A, Knoers N, Van Os C, Deen P. Aquaporin 2 mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008;28:252-65 pubmed publisher
    ..This review describes the current knowledge on AQP2 mutations in nephrogenic diabetes insipidus...
  8. Noda Y, Sasaki S. Trafficking mechanism of water channel aquaporin-2. Biol Cell. 2005;97:885-92 pubmed
    ..This review summarizes recent advances related to the trafficking mechanisms of AQP2. ..
  9. Kennedy C, Xiong H, Rahal S, Vanderluit J, Slack R, Zhang Y, et al. Urine concentrating defect in prostaglandin EP1-deficient mice. Am J Physiol Renal Physiol. 2007;292:F868-75 pubmed
    ..These data suggest that PGE(2) modulates urine concentration by acting at EP(1) receptors, not in the collecting duct, but within the hypothalamus to promote AVP synthesis in response to acute WD. ..

More Information


  1. Hasler U, Jeon U, Kim J, Mordasini D, Kwon H, Feraille E, et al. Tonicity-responsive enhancer binding protein is an essential regulator of aquaporin-2 expression in renal collecting duct principal cells. J Am Soc Nephrol. 2006;17:1521-31 pubmed
    ..These findings demonstrate that in collecting duct principal cells, TonEBP plays a central role in regulating AQP2 expression by enhancing AQP2 gene transcription. ..
  2. Procino G, Barbieri C, Carmosino M, Tamma G, Milano S, De Benedictis L, et al. Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells. Pflugers Arch. 2011;462:753-66 pubmed publisher
    ..In conclusion, these results strongly suggest that fluvastatin, or other drugs of the statin family, may prove useful in the therapy of XNDI. ..
  3. de Bragança A, Moyses Z, Magaldi A. Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression. Nephrol Dial Transplant. 2010;25:3840-5 pubmed publisher
  4. Li C, Wang W, Rivard C, Lanaspa M, Summer S, Schrier R. Molecular mechanisms of angiotensin II stimulation on aquaporin-2 expression and trafficking. Am J Physiol Renal Physiol. 2011;300:F1255-61 pubmed publisher
    ..ANG II-induced AQP2 expression involves cAMP, PKC, PKA, and calmodulin signaling pathways via V2 and AT(1) receptors. ..
  5. Kim G, Choi N, Jung J, Song J, Lee C, Kang C, et al. Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2. Am J Physiol Renal Physiol. 2008;294:F702-9 pubmed publisher
    ..The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI...
  6. Hasler U, Nunes P, Bouley R, Lu H, Matsuzaki T, Brown D. Acute hypertonicity alters aquaporin-2 trafficking and induces a MAPK-dependent accumulation at the plasma membrane of renal epithelial cells. J Biol Chem. 2008;283:26643-61 pubmed publisher
    ..This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity. ..
  7. Balasubramanian L, Sham J, Yip K. Calcium signaling in vasopressin-induced aquaporin-2 trafficking. Pflugers Arch. 2008;456:747-54 pubmed
    ..All of them have been implicated in the regulation of aquaporin-2 trafficking and/or water permeability. ..
  8. Di Giusto G, Flamenco P, Rivarola V, Fernandez J, Melamud L, Ford P, et al. Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation. J Cell Biochem. 2012;113:3721-9 pubmed publisher
    ..demonstrated that in renal cortical collecting duct cells (RCCD(1)) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation...
  9. Vossenkamper A, Nedvetsky P, Wiesner B, Furkert J, Rosenthal W, Klussmann E. Microtubules are needed for the perinuclear positioning of aquaporin-2 after its endocytic retrieval in renal principal cells. Am J Physiol Cell Physiol. 2007;293:C1129-38 pubmed
    ..We also demonstrate that cAMP-signaling regulates the localization of Rab11-positive recycling endosomes in renal principal cells. ..
  10. Satake M, Ikarashi N, Ichikawa Y, Maniwa A, Toda T, Ito K, et al. The role of renal aquaporin 2 in the alleviation of dehydration associated with diabetic polyuria in KKAy mice. Life Sci. 2010;87:475-80 pubmed publisher
    ..In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model.
  11. Tamma G, Procino G, Mola M, Svelto M, Valenti G. Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking. Pflugers Arch. 2008;456:729-36 pubmed publisher
    ..Altogether, these data demonstrate that annexin-2 is required for cAMP-induced AQP2 exocytosis in renal cells. ..
  12. O Neill H, Lebeck J, Collins P, Kwon T, Frøkiaer J, Nielsen S. Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus. Nephrol Dial Transplant. 2008;23:1546-55 pubmed
  13. Sasaki S. Aquaporin 2: from its discovery to molecular structure and medical implications. Mol Aspects Med. 2012;33:535-46 pubmed publisher
    This review describes the discovery of rat aquaporin 2 AQP2 as a vasopressin-regulated water channel, and subsequent isolation of human AQP2...
  14. Takata K. Aquaporin-2 (AQP2): its intracellular compartment and trafficking. Cell Mol Biol (Noisy-le-grand). 2006;52:34-9 pubmed
    ..Some of AQP2 is excreted as exosomes. Actin cytoskeleton plays important roles in the trafficking of AQP2. Analyses of molecules found in AQP2-containing vesicles will shed light on the mechanism of AQP2 translocation. ..
  15. Takata K, Matsuzaki T, Tajika Y, Ablimit A, Hasegawa T. Localization and trafficking of aquaporin 2 in the kidney. Histochem Cell Biol. 2008;130:197-209 pubmed publisher
    ..Actin plays an important role in the intracellular trafficking of AQP2. Recent findings have shed light on the molecular basis that controls the trafficking of AQP2. ..
  16. Moeller H, Knepper M, Fenton R. Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane of collecting duct principal cells. Kidney Int. 2009;75:295-303 pubmed publisher
    ..Our results show that S269 phosphorylated aquaporin-2 is exclusively associated with the apical plasma membrane, where it escapes endocytosis to remain at the cell surface. ..
  17. Wang C, Ng C, Shi H, Liew H, Guo K, Zeng Q, et al. A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2. Mol Cell Biol. 2010;30:333-43 pubmed publisher
    ..Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice...
  18. Hasler U, Leroy V, Martin P, Feraille E. Aquaporin-2 abundance in the renal collecting duct: new insights from cultured cell models. Am J Physiol Renal Physiol. 2009;297:F10-8 pubmed publisher
    ..These examples illustrate how cross talk between various stimuli regulates AQP2 abundance in collecting duct principal cells and consequently contributes to maintenance of body water homeostasis. ..
  19. Procino G, Mastrofrancesco L, Mira A, Tamma G, Carmosino M, Emma F, et al. Aquaporin 2 and apical calcium-sensing receptor: new players in polyuric disorders associated with hypercalciuria. Semin Nephrol. 2008;28:297-305 pubmed publisher
    ..nephropathies associated with impaired urinary concentrating ability and in particular analyzes the role of aquaporin 2 in hypercalciuria, the most common metabolic abnormality in patients with nephrolithiasis...
  20. Russo L, McKee M, Brown D. Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney. Am J Physiol Renal Physiol. 2006;291:F246-53 pubmed
  21. Jensen A, Li C, Praetorius H, Nørregaard R, Frische S, Knepper M, et al. Angiotensin II mediates downregulation of aquaporin water channels and key renal sodium transporters in response to urinary tract obstruction. Am J Physiol Renal Physiol. 2006;291:F1021-32 pubmed
    ..In conclusion, candesartan prevents dysregulation of AQP2, sodium transporters, and development of polyuria seen in BUO. This strongly supports the view that candesartan protects kidney function in response to urinary tract obstruction. ..
  22. Umenishi F, Narikiyo T, Vandewalle A, Schrier R. cAMP regulates vasopressin-induced AQP2 expression via protein kinase A-independent pathway. Biochim Biophys Acta. 2006;1758:1100-5 pubmed
    ..These results therefore indicate that the effect of AVP stimulation to upregulate AQP2 expression involves a PKA-independent pathway. ..
  23. Lee Y, Song I, Jang K, Nielsen J, Frøkiaer J, Nielsen S, et al. Increased AQP2 targeting in primary cultured IMCD cells in response to angiotensin II through AT1 receptor. Am J Physiol Renal Physiol. 2007;292:F340-50 pubmed
    ..In conclusion, ANG II plays a role in the regulation of AQP2 targeting to the plasma membrane in IMCD cells through AT(1) receptor activation and potentiates the effect of dDAVP on AQP2 plasma membrane targeting. ..
  24. Hildenbrand A, Lalitkumar L, Nielsen S, Gemzell Danielsson K, Stavreus Evers A. Expression of aquaporin 2 in human endometrium. Fertil Steril. 2006;86:1452-8 pubmed
    ..AQP2 is present in the human endometrium. The expression of AQP2 appears to be cycle dependent and suggests a role for AQP2 in implantation, edema, and/or menstruation. ..
  25. Bustamante M, Hasler U, Leroy V, de Seigneux S, Dimitrov M, Mordasini D, et al. Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. J Am Soc Nephrol. 2008;19:109-16 pubmed
  26. Bou Matar R, Malik B, WANG X, Martin C, Eaton D, Sands J, et al. Protein abundance of urea transporters and aquaporin 2 change differently in nephrotic pair-fed vs. non-pair-fed rats. Am J Physiol Renal Physiol. 2012;302:F1545-53 pubmed publisher
    ..In this study, we test for changes in the abundance of urea transporters, aquaporin 2 (AQP2), Na-K-2Cl cotransporter 2 (NKCC2), and Na-Cl cotransporter (NCC), in non-pair-fed and pair-fed nephrotic ..
  27. Noda Y, Horikawa S, Kanda E, Yamashita M, Meng H, Eto K, et al. Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking. J Cell Biol. 2008;182:587-601 pubmed publisher
    ..These findings indicate a novel mechanism of channel protein trafficking, in which the channel protein itself critically regulates local actin reorganization to initiate its movement. ..
  28. Brown D, Hasler U, Nunes P, Bouley R, Lu H. Phosphorylation events and the modulation of aquaporin 2 cell surface expression. Curr Opin Nephrol Hypertens. 2008;17:491-8 pubmed publisher
    This review highlights the role of phosphorylation in the trafficking and targeting of aquaporin 2. Current knowledge will be put into the context of modulating the cell surface expression of aquaporin 2 by vasopressin in renal ..
  29. Iacobelli S, Addabbo F, Bonsante F, Procino G, Tamma G, Acito A, et al. Aquaporin-2 excretion and renal function during the 1st week of life in preterm newborn infants. Nephron Physiol. 2006;104:121-5 pubmed
  30. Graf F, Ludin P, Wenzler T, Kaiser M, Brun R, Pyana P, et al. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol. PLoS Negl Trop Dis. 2013;7:e2475 pubmed publisher
    ..b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol. ..
  31. Street J, Birkhoff W, Menzies R, Webb D, Bailey M, Dear J. Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells. J Physiol. 2011;589:6119-27 pubmed publisher
    ..the synthetic vasopressin analogue, desmopressin, did not affect exosomal flotillin-1 or TSG101 but increased aquaporin 2 (AQP2) in a dose- and time-dependent manner that was highly correlated with cellular AQP2 (exosomal AQP2 vs...
  32. Iacobelli S, Gouyon J, Bonsante F, Mastrofrancesco L, Svelto M, Valenti G. Aquaporin-2 urinary excretion in preterm infants: relationship to diuresis and vasopressin. Acta Physiol (Oxf). 2010;200:339-45 pubmed publisher
    ..Further investigations are required to elucidate the mechanisms underlying the strong association between diuresis and u-AQP2 excretion in early postnatal life. ..
  33. Goel M, Zuo C, Schilling W. Role of cAMP/PKA signaling cascade in vasopressin-induced trafficking of TRPC3 channels in principal cells of the collecting duct. Am J Physiol Renal Physiol. 2010;298:F988-96 pubmed publisher
    ..Taken together, these results demonstrate that AVP stimulation of V2 receptors in principal cells of the CD causes translocation of TRPC3 to the apical membrane via stimulation of the AC/cAMP/PKA signaling cascade. ..
  34. Lau K, Yang Y, Cook G, Wyatt R, Nishimura H. Control of aquaporin 2 expression in collecting ducts of quail kidneys. Gen Comp Endocrinol. 2009;160:288-94 pubmed publisher
    ..We have identified the gene sequence of an aquaporin 2 (AQP2)-homologue water channel in collecting ducts of kidneys from adult quail, Coturnix japonica...
  35. Chu J, Chung S, Lam A, Tam S, Chung S, Chow B. Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption. Mol Cell Biol. 2007;27:2499-511 pubmed
    b>Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp)...
  36. Suga H, Nagasaki H, Kondo T, Okajima Y, Suzuki C, Ozaki N, et al. Novel treatment for lithium-induced nephrogenic diabetes insipidus rat model using the Sendai-virus vector carrying aquaporin 2 gene. Endocrinology. 2008;149:5803-10 pubmed publisher
    ..Either of the genetic defects in vasopressin V2 receptor or the water channel aquaporin 2 (AQP2) cause the disease, which interfere the water reabsorption at the epithelium of the collecting duct...
  37. Hoffert J, Pisitkun T, Wang G, Shen R, Knepper M. Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc Natl Acad Sci U S A. 2006;103:7159-64 pubmed
  38. Lu H, Matsuzaki T, Bouley R, Hasler U, Qin Q, Brown D. The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells. Am J Physiol Renal Physiol. 2008;295:F290-4 pubmed publisher
    ..The potential role of S261 phosphorylation/dephosphorylation in vasopressin action remains to be determined. ..
  39. de Seigneux S, Nielsen J, Olesen E, Dimke H, Kwon T, Frøkiaer J, et al. Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney. Am J Physiol Renal Physiol. 2007;293:F87-99 pubmed
    ..The increased basolateral expression of AQP2 induced by aldosterone may play a significant role in water metabolism in conditions with increased sodium reabsorption in the CCD. ..
  40. Graffe C, Bech J, Pedersen E. Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans. Am J Physiol Renal Physiol. 2012;302:F264-75 pubmed publisher
    ..In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism. ..
  41. Lee J, Kim S, Kim J, Jeong M, Oh Y, Choi K. Increased expression of renal aquaporin water channels in spontaneously hypertensive rats. Kidney Blood Press Res. 2006;29:18-23 pubmed
    ..The urine was more concentrated with its volume decreased in SHR. The expression of AQP1-3 channels is increased in the kidney, in association with enhanced activity of the AVP/cAMP pathway, in SHR. ..
  42. Bouley R, Lu H, Nunes P, Da Silva N, McLaughlin M, Chen Y, et al. Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration. J Am Soc Nephrol. 2011;22:59-72 pubmed publisher
    ..This suggests that calcitonin has a potential therapeutic use in nephrogenic diabetes insipidus. ..
  43. Li S, McDill B, Kovach P, Ding L, Go W, Ho S, et al. Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress. Am J Physiol Cell Physiol. 2007;292:C1606-16 pubmed
    ..The coordinate regulation of AQP2 expression by both osmotic stress and calcium signaling appears to provide a means to integrate diverse extracellular signals into optimal cellular responses. ..
  44. Okutsu R, Rai T, Kikuchi A, Ohno M, Uchida K, Sasaki S, et al. AKAP220 colocalizes with AQP2 in the inner medullary collecting ducts. Kidney Int. 2008;74:1429-33 pubmed publisher
    During dehydration, protein kinase A phosphorylates aquaporin 2 (AQP2) at serine 256 and this is essential for apical membrane sorting of AQP2 in the collecting ducts...
  45. Zwang N, Hoffert J, Pisitkun T, Moeller H, Fenton R, Knepper M. Identification of phosphorylation-dependent binding partners of aquaporin-2 using protein mass spectrometry. J Proteome Res. 2009;8:1540-54 pubmed publisher
    ..These results suggest that phosphorylation of AQP2 at Ser-256 may regulate AQP2 trafficking in part by mediating differential binding of hsp70 family proteins to the COOH-terminal tail. ..
  46. van Balkom B, Boone M, Hendriks G, Kamsteeg E, Robben J, Stronks H, et al. LIP5 interacts with aquaporin 2 and facilitates its lysosomal degradation. J Am Soc Nephrol. 2009;20:990-1001 pubmed publisher
    ..binding to the V2 receptor in renal principal cells leads to activation of protein kinase A, phosphorylation of aquaporin 2 (AQP2) at Ser256, and the translocation of AQP2 to the apical membrane, resulting in concentration of the urine...
  47. Noda Y, Sasaki S. Regulation of aquaporin-2 trafficking and its binding protein complex. Biochim Biophys Acta. 2006;1758:1117-25 pubmed
    ..In addition, a multiprotein "force generator" complex which directly binds to AQP2 has been discovered. This review summarizes recent advances related to the mechanism for AQP2 trafficking. ..
  48. Hoffert J, Nielsen J, Yu M, Pisitkun T, Schleicher S, Nielsen S, et al. Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term vasopressin treatment in collecting duct. Am J Physiol Renal Physiol. 2007;292:F691-700 pubmed
  49. Lauridsen T, Vase H, Starklint J, Bech J, Pedersen E. Protein-enriched diet increases water absorption via the aquaporin-2 water channels in healthy humans. Nephrol Dial Transplant. 2010;25:2502-10 pubmed publisher
    ..The increased u-AQP2 might be due to a reduced prostaglandin level. The increase in renal sodium excretion seems to be mediated in another part of the nephron than the epithelial sodium channels. ..
  50. Kamsteeg E, Duffield A, Konings I, Spencer J, Pagel P, Deen P, et al. MAL decreases the internalization of the aquaporin-2 water channel. Proc Natl Acad Sci U S A. 2007;104:16696-701 pubmed
    ..Thus, the involvement of MAL in the cell surface retention of apical membrane proteins could play an important role in regulated absorption and secretion in transporting epithelia. ..
  51. Yang B, Zhao D, Qian L, Verkman A. Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion. Am J Physiol Renal Physiol. 2006;291:F465-72 pubmed
  52. Cheong H, Cho S, Zheng S, Cho H, Ha I, Choi Y. Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus. J Korean Med Sci. 2005;20:1076-8 pubmed
  53. Renkema K, Velic A, Dijkman H, Verkaart S, van der Kemp A, Nowik M, et al. The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis. J Am Soc Nephrol. 2009;20:1705-13 pubmed publisher
    ..of the renal Ca(2+)-sensing receptor promoted H(+)-ATPase-mediated H(+) excretion and downregulation of aquaporin 2, leading to urinary acidification and polyuria, respectively...