aquaporin 6


Summary: Aquaporin 6 is an aquaglyceroporin that is found primarily in KIDNEY COLLECTING DUCTS. AQP6 protein functions as an anion-selective channel.

Top Publications

  1. Jeremic A, Cho W, Jena B. Involvement of water channels in synaptic vesicle swelling. Exp Biol Med (Maywood). 2005;230:674-80 pubmed
    ..Results from the study demonstrate that water channels AQP1 and AQP6, and the heterotrimeric Go protein are associated with SVs and participate in their swelling. ..
  2. Kamsteeg E, Heijnen I, Van Os C, Deen P. The subcellular localization of an aquaporin-2 tetramer depends on the stoichiometry of phosphorylated and nonphosphorylated monomers. J Cell Biol. 2000;151:919-30 pubmed
  3. Nielsen S, Chou C, Marples D, Christensen E, Kishore B, Knepper M. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci U S A. 1995;92:1013-7 pubmed
    ..We conclude that vasopressin increases the water permeability of collecting duct cells by inducing a reversible translocation of AQP-CD water channels from IVs to the APM. ..
  4. Rabaud N, Song L, Wang Y, Agre P, Yasui M, Carbrey J. Aquaporin 6 binds calmodulin in a calcium-dependent manner. Biochem Biophys Res Commun. 2009;383:54-7 pubmed publisher
    b>Aquaporin 6 (AQP6) is an anion channel that is expressed primarily in acid secreting alpha-intercalated cells of the kidney collecting duct. In addition, AQP6 anion channel permeability is gated by low pH...
  5. Nagase H, Agren J, Saito A, Liu K, Agre P, Hazama A, et al. Molecular cloning and characterization of mouse aquaporin 6. Biochem Biophys Res Commun. 2007;352:12-6 pubmed
    ..Functional analyses of water and ion permeation revealed that mAQP6a functions like rat AQP6 and that mAQP6b does not function as either a water channel or an ion channel under our experimental conditions. ..
  6. Marr N, Bichet D, Hoefs S, Savelkoul P, Konings I, de Mattia F, et al. Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol. 2002;13:2267-77 pubmed
    ..In addition, the reduced single channel water permeability of AQP2-A47V (40%) and AQP2-T125M (25%) might become of therapeutic value when chemical chaperones can be found that restore their routing to the plasma membrane. ..
  7. Chou C, Yip K, Michea L, Kador K, Ferraris J, Wade J, et al. Regulation of aquaporin-2 trafficking by vasopressin in the renal collecting duct. Roles of ryanodine-sensitive Ca2+ stores and calmodulin. J Biol Chem. 2000;275:36839-46 pubmed
    ..The results suggest that Ca(2+) release from ryanodine-sensitive stores plays an essential role in vasopressin-mediated aquaporin-2 trafficking via a calmodulin-dependent mechanism. ..
  8. Deen P, van Balkom B, Savelkoul P, Kamsteeg E, Van Raak M, Jennings M, et al. Aquaporin-2: COOH terminus is necessary but not sufficient for routing to the apical membrane. Am J Physiol Renal Physiol. 2002;282:F330-40 pubmed
    ..The study shows that the AQP2 COOH tail is necessary but not sufficient for routing to the AM and suggests that other parts of AQP2 are needed for AQP2 accumulation in intracellular vesicles. ..
  9. van Balkom B, Savelkoul P, Markovich D, Hofman E, Nielsen S, van der Sluijs P, et al. The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J Biol Chem. 2002;277:41473-9 pubmed

More Information


  1. Hazama A, Kozono D, Guggino W, Agre P, Yasui M. Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation. J Biol Chem. 2002;277:29224-30 pubmed
  2. Kishore B, Krane C, Di Iulio D, Menon A, Cacini W. Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria. Kidney Int. 2000;58:701-11 pubmed
    ..Cisplatin (CP)-induced polyuria in rats is attributed to decreased medullary hypertonicity and/or an end-organ resistance to vasopressin. However, the roles of renal aquaporins (AQPs) have not yet been explored...
  3. Inoue T, Nielsen S, Mandon B, Terris J, Kishore B, Knepper M. SNAP-23 in rat kidney: colocalization with aquaporin-2 in collecting duct vesicles. Am J Physiol. 1998;275:F752-60 pubmed
    ..However, localization of SNAP-23 in both intracytoplasmic vesicles and plasma membranes suggests a function different from that originally proposed for SNAP-25 in synaptic vesicle targeting. ..
  4. Mulders S, Bichet D, Rijss J, Kamsteeg E, Arthus M, Lonergan M, et al. An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest. 1998;102:57-66 pubmed
    ..Since AQPs are thought to tetramerize, the retention of AQP2-E258K together with wild-type AQP2 in mixed tetramers in the Golgi compartment is a likely explanation for the dominant inheritance of NDI in this patient...
  5. Fushimi K, Sasaki S, Marumo F. Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel. J Biol Chem. 1997;272:14800-4 pubmed
    ..Our results indicated that serine 256 of AQP2 is necessary for regulatory exocytosis and that cAMP-responsive redistribution of AQP2 may be regulated by phosphorylation of AQP2. ..
  6. Nielsen S, Frør J, Knepper M. Renal aquaporins: key roles in water balance and water balance disorders. Curr Opin Nephrol Hypertens. 1998;7:509-16 pubmed
    ..In this review, we focus mainly on the vasopressin-regulated water channel, aquaporin 2, and its critical role in acute and chronic regulation of body water balance, as well as in multiple water balance disorders. ..
  7. Ma T, Yang B, Kuo W, Verkman A. cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: evidence for a gene cluster of aquaporins at chromosome locus 12q13. Genomics. 1996;35:543-50 pubmed
    ..Further work is needed to establish the physiological significance of hKID. ..
  8. Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, et al. Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet. 2001;69:738-48 pubmed
    ..Segregation of the mutations in the C-terminus of AQP2 with dominant-type NDI underlies the importance of this domain in the intracellular trafficking of AQP2...
  9. Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, et al. Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int. 2003;64:2-10 pubmed
    ..The Xenopus oocyte expression study suggested that the trafficking of the mutant AQP2s was impaired...
  10. Ikeda M, Beitz E, Kozono D, Guggino W, Agre P, Yasui M. Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem. 2002;277:39873-9 pubmed
  11. Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993;361:549-52 pubmed
    ..The functional expression and the limited localization of WCH-CD to the apical region of the kidney collecting tubule suggest that WCH-CD is the vasopressin-regulated water channel. ..
  12. Taguchi D, Takeda T, Kakigi A, Okada T, Nishioka R, Kitano H. Expression and immunolocalization of aquaporin-6 (Aqp6) in the rat inner ear. Acta Otolaryngol. 2008;128:832-40 pubmed publisher
    ..However, its lack of expression on the plasma membrane indicates that Aqp6 does not have a direct role in water flux via the plasma membrane...
  13. Yasui M, Kwon T, Knepper M, Nielsen S, Agre P. Aquaporin-6: An intracellular vesicle water channel protein in renal epithelia. Proc Natl Acad Sci U S A. 1999;96:5808-13 pubmed
    ..Moreover, our studies predict that AQP6 participates in distinct physiological functions such as glomerular filtration, tubular endocytosis, and acid-base metabolism. ..
  14. Klussmann E, Maric K, Wiesner B, Beyermann M, Rosenthal W. Protein kinase A anchoring proteins are required for vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells. J Biol Chem. 1999;274:4934-8 pubmed
    ..These data demonstrate that not only the activity of PKA, but also its tethering to subcellular compartments, are prerequisites for cAMP-dependent AQP-2 translocation. ..
  15. Matsuki Fukushima M, Hashimoto S, Shimono M, Satoh K, Fujita Yoshigaki J, Sugiya H. Presence and localization of aquaporin-6 in rat parotid acinar cells. Cell Tissue Res. 2008;332:73-80 pubmed publisher
    ..These results suggest that AQP6 participates in water and anion transport in plasma membranes near tight junctions and secretory granule membranes in rat parotid acinar cells. ..
  16. Deen P, Knoers N. Physiology and pathophysiology of the aquaporin-2 water channel. Curr Opin Nephrol Hypertens. 1998;7:37-42 pubmed
    ..Because of its importance for normal water homeostasis and its involvement in many water balance disorders, aquaporin-2, the predominant vasopressin-regulated water channel of the renal collecting duct, is discussed in detail. ..
  17. Deen P, Verdijk M, Knoers N, Wieringa B, Monnens L, Van Os C, et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science. 1994;264:92-5 pubmed
    ..Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine...
  18. Valenti G, Procino G, Carmosino M, Frigeri A, Mannucci R, Nicoletti I, et al. The phosphatase inhibitor okadaic acid induces AQP2 translocation independently from AQP2 phosphorylation in renal collecting duct cells. J Cell Sci. 2000;113 ( Pt 11):1985-92 pubmed
    ..Thus AQP2 phosphorylation is not essential for water channel translocation in renal cells, indicating that different pathways might exist leading to AQP2 apical insertion and increase in P(f). ..
  19. Liu K, Kozono D, Kato Y, Agre P, Hazama A, Yasui M. Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci U S A. 2005;102:2192-7 pubmed
    ..We propose that the asparagine residue at the contact point between TM2 and TM5 in AQP6 may function as a teeter board needed for rapid structural oscillations during anion permeation. ..
  20. Mandon B, Chou C, Nielsen S, Knepper M. Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking. J Clin Invest. 1996;98:906-13 pubmed
  21. Ma T, Frigeri A, Skach W, Verkman A. Cloning of a novel rat kidney cDNA homologous to CHIP28 and WCH-CD water channels. Biochem Biophys Res Commun. 1993;197:654-9 pubmed
    ..WCH3 is a new member of the MIP26 family of channel-forming proteins in mammalian kidney. ..
  22. Nyul Z, Vajda Z, Vida G, Sulyok E, Frokiaer J, Nielsen S. Urinary aquaporin-2 excretion in preterm and full-term neonates. Biol Neonate. 2002;82:17-21 pubmed
    ..It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine. ..
  23. Martin P, Bianchi M, Roger F, Niksic L, Feraille E. Arginine vasopressin modulates expression of neuronal NOS in rat renal medulla. Am J Physiol Renal Physiol. 2002;283:F559-68 pubmed
    ..Because nNOS is specifically expressed in principal cells of the collecting duct system, the stimulation of nNOS expression by AVP may participate in the control of water reabsorption. ..
  24. Wang W, Li C, Kwon T, Knepper M, Frøkiaer J, Nielsen S. AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. Am J Physiol Renal Physiol. 2002;283:F1313-25 pubmed
    ..Moreover, PDE inhibitor treatment significantly prevented the reduced expression of collecting duct AQPs and prevented the development of polyuria. ..
  25. Kamsteeg E, Bichet D, Konings I, Nivet H, Lonergan M, Arthus M, et al. Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus. J Cell Biol. 2003;163:1099-109 pubmed
    ..Our data reveal a novel cellular phenotype in dominant NDI and show that dominance of basolateral sorting motifs in a mutant subunit can be the molecular basis for disease. ..
  26. Warshel A. Inverting the selectivity of aquaporin 6: gating versus direct electrostatic interaction. Proc Natl Acad Sci U S A. 2005;102:1813-4 pubmed
  27. Shin L, Basi N, Jeremic A, Lee J, Cho W, Chen Z, et al. Involvement of vH(+)-ATPase in synaptic vesicle swelling. J Neurosci Res. 2010;88:95-101 pubmed publisher
    ..Vesicle acidification is therefore a prerequisite for AQP-6-mediated gating of water into synaptic vesicles. ..
  28. Davis I, MacRae Dell K. Are aquaporin water channels the "holy grail" of primary nocturnal enuresis?. J Urol. 2002;167:1451-2 pubmed
  29. Knepper M, Inoue T. Regulation of aquaporin-2 water channel trafficking by vasopressin. Curr Opin Cell Biol. 1997;9:560-4 pubmed
    ..The vesicle-targeting proteins synaptobrevin-2 and syntaxin-4 are proposed to play roles in this process. ..
  30. Kusaka I, Saito T, Nakamura T, Nagasaka S, Ishibashi S, Ishikawa S. Urinary excretion of aquaporin-2 water channel in diabetic ketoacidosis. Nephron. 2002;91:167-9 pubmed
  31. Combet S, Teillet L, Geelen G, Pitrat B, Gobin R, Nielsen S, et al. Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2. Am J Physiol Renal Physiol. 2001;281:F1123-31 pubmed
  32. Kim D, Sands J, Klein J. Changes in renal medullary transport proteins during uncontrolled diabetes mellitus in rats. Am J Physiol Renal Physiol. 2003;285:F303-9 pubmed
    ..UT-B and ROMK were unchanged at any time point. The increases in UT-A1, AQP2, and NKCC2/BSC1 proteins during uncontrolled DM would tend to limit the loss of fluid and solute during uncontrolled diabetes. ..
  33. Masuda S, Hattori A, Matsumoto H, Miyazawa S, Natori Y, Mizutani S, et al. Involvement of the V2 receptor in vasopressin-stimulated translocation of placental leucine aminopeptidase/oxytocinase in renal cells. Eur J Biochem. 2003;270:1988-94 pubmed
  34. Downey P, Sapirstein A, O LEARY E, Sun T, Brown D, Bonventre J. Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2). Am J Physiol Renal Physiol. 2001;280:F607-18 pubmed
    ..Thus mice lacking cPLA(2) develop an age-related defect in renal concentration that may be related to abnormal trafficking and/or folding of AQP1 in the proximal tubule, implicating cPLA(2) in these processes...
  35. Pedersen R, Bentzen H, Bech J, Pedersen E. Effect of water deprivation and hypertonic saline infusion on urinary AQP2 excretion in healthy humans. Am J Physiol Renal Physiol. 2001;280:F860-7 pubmed
    ..83; P < 0.0001). It can be concluded that p-AVP and u-AQP2 are increased during thirst and hypertonic saline infusion and that u-AQP2 reflects the action of AVP on the collecting ducts...
  36. Brion L, Suarez C, Saenger P. Postnatal disappearance of type A intercalated cells in carbonic anhydrase II-deficient mice. Pediatr Nephrol. 2001;16:477-81 pubmed
    ..AE1-positive cells accounted for the majority of intercalated cells in the OMCD. The mechanisms leading to selective postnatal cell depletion in the collecting duct in CAD mice remain to be determined. ..
  37. Holm L, Klaerke D, Zeuthen T. Aquaporin 6 is permeable to glycerol and urea. Pflugers Arch. 2004;448:181-6 pubmed
    ..There were no significant uptakes in native oocytes nor in AQP1-expressing oocytes whether these were treated with HgCl(2) or not. We conclude that water, glycerol and urea share an aqueous pathway in AQP6. ..
  38. Lu H, Sun T, Bouley R, Blackburn K, McLaughlin M, Brown D. Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. Am J Physiol Renal Physiol. 2004;286:F233-43 pubmed
  39. Yusenko M, Zubakov D, Kovacs G. Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours. Int J Biol Sci. 2009;5:517-27 pubmed
  40. Cluzeaud F, Reyes R, Escoubet B, Fay M, Lazdunski M, Bonvalet J, et al. Expression of TWIK-1, a novel weakly inward rectifying potassium channel in rat kidney. Am J Physiol. 1998;275:C1602-9 pubmed
  41. Franki N, Macaluso F, Schubert W, Gunther L, Hays R. Water channel-carrying vesicles in the rat IMCD contain cellubrevin. Am J Physiol. 1995;269:C797-801 pubmed
    ..Cellubrevin, therefore, is in a position to mediate one or more steps in arginine vasopressin-induced water channel cycling...
  42. Kuwahara M. Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus. Intern Med. 1998;37:215-7 pubmed
    ..Our results suggest that T125M and G175R are nonfunctional water channels, whereas the translocation to the plasma membrane is impaired in A190T and P262L...
  43. El Dahr S, Harrison Bernard L, Dipp S, Yosipiv I, Meleg Smith S. Bradykinin B2 null mice are prone to renal dysplasia: gene-environment interactions in kidney development. Physiol Genomics. 2000;3:121-31 pubmed
    ..This study provides a "proof-of-principle" that defined gene-environment interactions are a cause of congenital renal disease...
  44. Amlal H, Wilke C. Resistance of mTAL Na+-dependent transporters and collecting duct aquaporins to dehydration in 7-month-old rats. Kidney Int. 2003;64:544-54 pubmed
    ..This defect results from reduced responsiveness of cortical AQP2 and AQP3 and a blunted response of medullary AQP2 and mTAL BSC1, NHE3, and Na+ pump to dehydration in aging kidneys. ..
  45. Hill W, Kaetzel M, Kishore B, Dedman J, Zeidel M. Annexin A4 reduces water and proton permeability of model membranes but does not alter aquaporin 2-mediated water transport in isolated endosomes. J Gen Physiol. 2003;121:413-25 pubmed
    ..We conclude that Anx4 can alter the physical properties of membranes by associating with them and regulate passive membrane permeability to water and protons. These properties represent important new functions for Anx4. ..
  46. Tanaka Y, Sugita K, Saito T, Muroya K, Ishikawa S, Awazu M, et al. Impaired urinary water excretion in a three-generation family. Pediatr Nephrol. 2001;16:820-2 pubmed
    ..2 +/- 7.8%). Urinary AQP2 excretion was normal, as was the DNA sequence of AVPR2 and AQP2. The results suggest the presence of a new dominantly inherited disorder for tubular water resorption. ..
  47. Moiseev S, Fomin V. [Nephrological aspects of congestive cardiac failure]. Ter Arkh. 2003;75:84-9 pubmed
  48. Hagstrøm S, Siggaard C, Kamperis K, Christensen J, Rittig S. [Congenital nephrogenic diabetes insipidus. A four-month-old girl with delayed psychomotor development]. Ugeskr Laeger. 2005;167:1759-61 pubmed
  49. Smith A, Finberg K, Wagner C, Lifton R, Devonald M, Su Y, et al. Molecular cloning and characterization of Atp6n1b: a novel fourth murine vacuolar H+-ATPase a-subunit gene. J Biol Chem. 2001;276:42382-8 pubmed
  50. Umenishi F, Summer S, Cadnapaphornchai M, Schrier R. Comparison of three methods to quantify urinary aquaporin-2 protein. Kidney Int. 2002;62:2288-93 pubmed
    ..Also, urinary AQP2 was positively correlated with urine osmolality among all three methods. The results indicate that the newly developed IB and ELISA methods are useful for measurement of urinary AQP2 and have an excellent correlation. ..
  51. Fernandez Llama P, Turner R, Dibona G, Knepper M. Renal expression of aquaporins in liver cirrhosis induced by chronic common bile duct ligation in rats. J Am Soc Nephrol. 1999;10:1950-7 pubmed
    ..Thus, dysregulation of multiple water channels and ion transporters may play a role in water balance abnormalities associated with CBDL-induced cirrhosis in rats. ..
  52. Klein J, Gunn R, Roberts B, Sands J. Down-regulation of urea transporters in the renal inner medulla of lithium-fed rats. Kidney Int. 2002;61:995-1002 pubmed
    ..Decreases in UT-A1, UT-B, and AQP2 protein abundance, and/or vasopressin-stimulated phosphorylation of UT-A1, can contribute to the reduced urine concentrating ability that occurs in lithium-treated rats. ..
  53. Stanhope M, Madsen O, Waddell V, Cleven G, de Jong W, Springer M. Highly congruent molecular support for a diverse superordinal clade of endemic African mammals. Mol Phylogenet Evol. 1998;9:501-8 pubmed publisher
    ..The majority of the data sets and analyses provide strong support for Caviomorpha as part of a monophyletic Rodentia...