Water Channels

Kidney International (1995) 48, 1057–1068; doi:10.1038/ki.1995.389

The aquaporin family of water channels in kidney

Søren Nielsen and Peter Agre

Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark, and Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland, USA; and Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, and Mt. Desert Island Biological Laboratory, Salisbury Cove, Maine, USA

Correspondence: Søren Nielsen MD PhD, Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark.

Top

Abstract

The aquaporin family of water channels in kidney. The longstanding puzzle of membrane water permeability was advanced by the discovery of channel-forming integral protein (CHIP). This protein was shown to function as a water channel when expressed in Xenopus oocytes or when reconstituted into synthetic membranes. Site-directed mutagenesis and electron crystallography reveal tetrameric organization of CHIP, and the two halves of CHIP are tandem repeats folded into an obversely symmetric structure which resembles an hourglass. Each tetramer is comprised of functionally independent subunits. CHIP is the archetypal member of a newly-recognized family of membrane water transporters known as the "Aquaporins" (AQPs). AQP1 (CHIP) is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in a number of extra renal tissues. In the collecting duct, AQP2 is the predominant vasopressin-sensitive water channel. AQP2 is loclized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by antidiuretic hormone. Humans are identified with mutations in AQP1 and AQP2 and exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of collecting duct principal cells providing an exit pathway for water, and AQP4 is abundant in brain, where it apparently functions as the hypothalamic osmoreceptor responsible for secretion of antidiuretic hormone. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and water balance disorders.

Top

References

  1. Finkelstein A: Water Movement Through Lipid Bilayers, Pores, and Plasma Membranes, Theory and Reality. New York, John Wiley & Sons, 1987
  2. Knepper MA, Rector FC, Jr: Urinary concentration and dilution, in The Kidney, edited by Brenner BM, Rector FC Jr, Philadelphia, London, W.B. Saunders Company, 1991, p 445
  3. Solomon AK, Chasan B, Dix JA, Lukacovic MF, Toon MR, Verkman AS: The aqueous pore in the red cell membrane: Band 3 as a channel for anions, cations, nonelectrolytes, and water. Ann NY Acad Sci 414:97–124, 1983
  4. MacEy RI: Transport of water and urea in red blood cells. Am J Physiol 246:C195–C203, 1984 | PubMed | ChemPort |
  5. Harris HWJ, Strange K, Zeidel ML: Current understanding of the cellular biology and molecular structure of the antidiuretic hormonestimulated water transport pathway. J Clin Invest 88:1–8, 1991 | PubMed | ChemPort |
  6. Verkman AS: Mechanisms and regulation of water permeability in renal epithelia. Am J Physiol 257:C837–C850, 1989
  7. Agre P, Preston GM, Smith BL, Jung JS, Raina S, Moon C, Guggino WB, Nielsen S: Aquaporin CHIP: The archetypal molecular water channel. Am J Physiol 265:F463–F476, 1993 | PubMed | ISI | ChemPort |
  8. Knepper MA: The aquaporin family of molecular water channels. Proc Natl Acad Sci USA 91:6255–6258, 1994 | PubMed | ChemPort |
  9. 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. J Biol Chem 263:15634–15642, 1988 | PubMed | ISI | ChemPort |
  10. Smith BL, Agre P: Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. J Biol Chem 266:6407–6415, 1991 | PubMed | ISI | ChemPort |
  11. Preston GM, Agre P: Isolation of the cDNA for erythrocyte integral membrane protein of 28 kD: Member of an ancient channel family. Proc Natl Acad Sci USA 88:11110–11114, 1991 | Article | PubMed | ChemPort |
  12. Preston GM, Carroll TP, Guggino WB, Agre P: Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 256:385–387, 1992 | Article | PubMed | ISI | ChemPort |
  13. Zeidel ML, Ambudkar SV, Smith BL, Agre P: Reconstitution of functional water channels in liposomes containing purified red cell CHIP28 protein. Biochemistry 31:7436–7440, 1992 | Article | PubMed | ISI | ChemPort |
  14. Deen PM, Dempster JA, Wieringa B, Van Os CH: Isolation of a cDNA for rat CHIP28 water channel: High mRNA expression in kidney cortex and inner medulla. Biochem Biophys Res Commun 188:1267–1273, 1992
  15. Van Hoek AN, Verkman AS: Functional reconstitution of the isolated erythrocyte water channel CHIP28. J Biol Chem 267:18267–18269, 1992 | PubMed | ChemPort |
  16. Zhang R, Skach W, Hasegawa H, Van Hoek AN, Verkman AS: Cloning, functional analysis and cell localization of a kidney proximal tubule water transporter homologous to CHIP28. Cell Biol 120:359–369, 1993
  17. Echevarria M, Frindt G, Preston GM, Milovanovic S, Agre P, Fischbarg J, Windhager EE: Expression of multiple water channel activities in Xenopus oocytes injected with mRNA from rat kidney. J Gen Physiol 101:827–841, 1993
  18. Engel A, Walz T, Agre P: Structure of the aquaporin water channels. Curr Opin Struct Biol 4:545–553, 1994 | ISI | ChemPort |
  19. Wistow GJ, Pisano MM, Chepelinsky AB: Tandem sequence repeats in transmembrane channel proteins. Trends Biochem Sci 16:170–171, 1991 | Article | PubMed | ISI | ChemPort |
  20. Reizer J, Reizer A, Saier MHJ: The MIP family of integral membrane channel proteins: Sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins. Crit Rev Biochem Mol Biol 28:235–257, 1993 | PubMed | ISI | ChemPort |
  21. Preston GM, Jung JS, Guggino WB, Agre P: The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel. J Biol Chem 268:17–20, 1993 | PubMed | ISI | ChemPort |
  22. Jung JS, Preston GM, Smith BL, Guggino WB, Agre P: Molecular structure of the water channel through Aquaporin CHIP: The hourglass model. J Biol Chem 269:14648–14654, 1994 | PubMed | ISI | ChemPort |
  23. Verbavatz JM, Brown D, Sabolic I, Valenti G, Ausiello DA, Van Hoek AN, Ma T, Verkman AS: Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: A freeze-fracture study. J Cell Biol 123:605–618, 1993 | Article | PubMed | ISI | ChemPort |
  24. Zeidel ML, Nielsen S, Smith BL, Ambudkar SV, Maunsbach AB, Agre P: Ultrastructure, pharmacologic inhibition, and transport selectivity of Aquaporin channel-forming integral protein in proteoliposomes. Biochemistry 33:1606–1615, 1994 | PubMed | ISI | ChemPort |
  25. Van Hoek AN, Hom ML, Luthjens LH, De Jong MD, Dempster JA, Van Os CH: Functional unit of 30 kD for proximal tubule water channels as revealed by radiation inactivation. J Biol Chem 266:16633–16635, 1991 | PubMed | ChemPort |
  26. Walz T, Smith BL, Zeidel ML, Engel A, Agre P: Biologically active two-dimensional crystals of aquaporin CHIP. J Biol Chem 269:1583–1586, 1994 | PubMed | ISI | ChemPort |
  27. Walz T, Smith BL, Agre P, Engel A: The three-dimensional structure of human erythrocyte aquaporin CHIP. EMBO J 13:2985–2993, 1994 | PubMed | ISI | ChemPort |
  28. Gorin MB, Yancey SB, Cline J, Revel JP, Horwitz J: The major intrinsic protein (MIP) of the bovine lens fiber membrane: Characterization and structure based on cDNA cloning. Cell 39:49–59, 1984 | Article | PubMed | ISI | ChemPort |
  29. Ehring GR, Zampighi G, Horwitz J, Bok D, Hall JE: Properties of channels reconstituted from the major intrinsic protein of lens fiber membranes. J Gen Physiol 96:631–664, 1990 | Article | ChemPort |
  30. Agre P, Sasaki S, Chrispeels MJ: Aquaporins: A family of water channel proteins. Am J Physiol 265:F461, 1993 | ChemPort |
  31. 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 361:549–552, 1993 | Article | PubMed | ISI | ChemPort |
  32. Ishibashi K, Sasaki S, Fushimi K, Uchida S, Kuwahara M, Saito H, Furukawa T, Nakajima K, Yamaguchi Y, Gojobori T, Marumo F: Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc Natl Acad Sci USA 91:6269–6273, 1994 | PubMed | ChemPort |
  33. Jung JS, Bhat V, Preston GM, Guggino WB, Baraban JM, Agre P: Molecular characterization of an Aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci USA 91:13052–13056, 1994 | Article | PubMed | ChemPort |
  34. Nielsen S, Smith B, Christensen EI, Knepper MA, Agre P: CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. J Cell Biol 120:371–383, 1993 | Article | PubMed | ISI | ChemPort |
  35. Bond C, Chin E, Smith BL, Preston GM, Agre P: Developmental gene expression and tissue distribution of the CHIP28 water-channal protein. Proc Natl Acad Sci USA 90:4500–4504, 1993
  36. Hasegawa H, Zhang R, Dohrman A, Verkman AS: Tissue-specific expression of mRNA encoding rat kidney wather channel CHIP28 by in situ hybridization. Am J Physiol 264:C237–C245, 1993 | PubMed | ISI | ChemPort |
  37. Sabolic I, Valenti G, Verbavatz JM, Van Hoek AN, Verkman AS, Ausiello DA, Brown D: Localization of the CHIP28 water channel in rat kidney. Am J Physiol 263:C1225–C1233, 1992 | PubMed | ISI | ChemPort |
  38. Maunsbach AB, Christensen EI: Functional ultrastructure of the proximal tubule, in Handbook of Physiology—Renal Physiology, edited by Windhager EE, New York, Oxford University Press, 1992
  39. Nielsen S, Smith BL, Christensen EI, Agre P: Distribution of Aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci USA 90:7275–7279, 1993 | Article | PubMed | ChemPort |
  40. Chou CL, Knepper MA: In vitro perfusion of chinchilla thin limb segments: Segmentation and osmotic water permeability. Am J Physiol 263:F417–F426, 1992
  41. Chou CL, Nielsen S, Knepper MA: Structural-functional correlation in chinchilla long loop of Henle thin limbs: A novel papillary subsegment. Am J Physiol 265:F863–F874, 1993
  42. Nielsen S, Pallone TL, Smith BL, Christensen EI, Agre P, Maunsbach AB: Aquaporin-1 water channels in short and long loop descending thin limbs and in descending vasa recta in rat kidney. Am J Physiol 268:F1023–F1039, 1995 | ChemPort |
  43. Imai M, Hayashi M, Araki M: Functional heterogeneity of the descending limbs of Henle's loop. I. Internephron heterogeneity in the hamster kidney. Pflügers Arch 402:385–392, 1984 | Article | ChemPort |
  44. Pallone TL, Nielsen S, Silldorff EP, Yang S: Diffusive transport of solutes in the rat medullary microcirculation. Am J Physiol 269:F55–F63, 1995
  45. Berry CA, Rector FC Jr: Renal transport of glucose, amino acids, sodium, chloride, and water, in The Kidney, edited by Brenner BM, Rector Jr, Philadelphia, WB Saunders Company, 1991, p 245
  46. Maeda Y, Agre P, Smith BL, Knepper MA: Quantification of Aquaporin-CHIP water channel protein in microdissected renal tubules by fluorescence-based ELISA. J Clin Invest 95:422–428, 1995 | PubMed | ISI | ChemPort |
  47. Smith BL, Baumgarten R, Nielsen S, Raben D, Zeidel ML, Agre P: Concurrent expression of erythroid and renal aquaporin CHIP and appearance of water channel activity in perinatal rats [see comments]. J Clin Invest 92:2035–2041, 1993
  48. Agre P, Smith BL, Baumgarten R, Preston GM, Pressman E, Wilson P, Illum N, Anstee DJ, Lande MB, Zeidel ML: Human red cell Aquaporin CHIP. II. Expression during normal fetal developement and in a novel form of congenital dyserythropoetic anemia. J Clin Invest (in press)
  49. Nielsen S, Digiovanni SR, Christensen EI, Knepper MA, Harris HW: Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 90:11663–11667, 1993 | PubMed | ChemPort |
  50. Knepper MA, Nielsen S, Chou CL, Digiovanni SR: Mechanism of vasopressin action in the renal collecting duct. Semin Nephrol 14:302–321, 1994 | PubMed |
  51. Morel A, O'Carroll AM, Brownstein MJ, Lolait SJ: Molecular cloning and expression of a rat V1a arginine vasopressin receptor. Nature 356:523–526, 1992 | Article | PubMed | ISI | ChemPort |
  52. Dousa TP, Sands H, Hechter O: Cyclic AMP-dependent reversible phosphorylation of renal medullary plasma membrane protein. Endocrinology 91:757–763, 1972
  53. Star RA, Nonoguchi H, Balaban R, Knepper MA: Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct. J Clin Invest 81:1879–1888, 1988 | PubMed | ISI | ChemPort |
  54. Maeda Y, Terada Y, Nonoguchi H, Knepper MA: Hormone and autacoid regulation of cAMP production in rat IMCD subsegments. Am J Physiol 263:F319–F327, 1992 | PubMed | ISI | ChemPort |
  55. Han JS, Maeda Y, Knepper MA: Dual actions of vasopressin and oxytocin in regulation of water permeability in terminal collecting duct. Am J Physiol 265:F26–F34, 1993 | PubMed |
  56. Flamion B, Spring KR: Water permeability of apical and basolateral cell membranes of rat inner medullary collecting duct. Am J Physiol 259:F986–F999, 1990
  57. Wall SM, Han JS, Chou CL, Knepper MA: Kinetics of urea and water permeability activation by vasopressin in rat terminal IMCD. Am J Physiol 262:F989–F998, 1992
  58. Kuwahara M, Shi LB, Marumo F, Verkman AS: Transcellular water flow modulates water channel exocytosis and endocytosis in kidney collecting tubule. J Clin Invest 88:423–429, 1991
  59. Nielsen S, Knepper MA: Vasopressin activates collecting duct urea transporters and water channels by distinct physical processes. Am J Physiol 265:F204–F213, 1993 | PubMed |
  60. Ma T, Hasewgawa H, Skach WR, Frigeri A, Verkman AS: Expression, functional analysis, and in situ hybridization of a cloned rat kidney collecting duct water channel. Am J Physiol 266:C189–C197, 1994 | PubMed | ISI | ChemPort |
  61. Wade JB, Stetson DL, Lewis SA: ADH action: Evidence for a membrane shuttle mechanism. Ann NY Acad Sci 372:106–117, 1981 | Article | PubMed | ChemPort |
  62. Kachadorian WA, Wade JB, Discala VA: Vasopressin: Induced structural change in toad bladder luminal membrane. Science 190:67–69, 1975 | PubMed | ChemPort |
  63. Kachadorian WA, Levine SD, Wade JB, Di-Scala VA, Hays RM: Relationship of aggregated intramembranous particles to water permeability in vasopressin-treated toad urinary bladder. J Clin Invest 59:576–581, 1977 | PubMed | ISI | ChemPort |
  64. Harmanci MC, Kachadorian WA, Valtin H, Discala VA: Antidiuretic hormone-induced intramembranous alterations in mammalian collecting ducts. Am J Physiol 235:440–443, 1978
  65. Wade JB: Role of membrane traffic in the water and Na responses to vasopressin. Semin Nephrol 14:322–332, 1994
  66. Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA: Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA 92:1013–1017, 1995 | PubMed | ChemPort |
  67. Knepper MA, Han KS, Maeda Y, Ecelbarger C, Digiovanni SR, Chou CL, Nielsen S, Wade JB: Vasopressin-independent regulation of collecting duct water permeability: Long-term versus short-term factors. Vasopressin 14:381–391, 1993
  68. Lankford SP, Chou CL, Terada Y, Wall SM, Wade JB, Knepper MA: Regulation of collecting duct water permeability independent of cAMP-mediated AVP response. Am J Physiol 261:F554–F566, 1991 | ChemPort |
  69. Wade JB, Nielsen S, Coleman RA, Knepper MA: Long-term regulation of collecting duct water permeability: Freeze-fracture analysis of isolated perfused tubules. Am J Physiol 266:F723–F730, 1994
  70. Digiovanni SR, Nielsen S, Christensen EI, Knepper MA: Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. Proc Natl Acad Sci USA 91:8984–8988, 1994 | Article | PubMed | ChemPort |
  71. You G, Smith CP, Kanai Y, Lee WS, Stelzner M, Hediger MA: Cloning and characterization of the vasopressin-regulated urea transporter. Nature 365:844–847, 1993 | Article | PubMed | ISI | ChemPort |
  72. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS: Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J Biol Chem 269:5497–5500, 1994 | PubMed | ISI | ChemPort |
  73. Oliet SH, Bourque CW: Mechanosensitive channels transduce osmosensitivity in supraoptic neurons. Nature 364:341–343, 1993 | Article | PubMed | ISI | ChemPort |
  74. Moon C, Preston GM, Griffin CA, Jabs EW, Agre P: The human aquaporin-CHIP gene: Structure, organization, and chromosomal localization. J Biol Chem 268:15772–15778, 1993 | PubMed | ChemPort |
  75. Zelinski T, Kaita H, Gilson T, Coghlan G, Philipps S, Lewis M: Linkage between the Colton blood group locus and ASSP11 on chromosome 7. Genomics 6:623–625, 1990
  76. Smith BL, Preston GM, Spring FA, Anstee DJ, Agre P: Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens. J Clin Invest 94:1043–1049, 1994 | PubMed | ISI | ChemPort |
  77. Preston GM, Smith BL, Zeidel ML, Moulds JJ, Agre P: Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels. Science 265:1585–1587, 1994 | Article | PubMed | ISI | ChemPort |
  78. Merendino JJJ, Speigel AM, Crawford JD, O'Carroll AM, Brownstein MJ, Lolait SJ: Brief report: a mutation in the vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus [see comments]. N Engl J Med 328:1538–1541, 1993
  79. Lolait SJ, O'Carroll AM, McBride OW, Konig M, Morel A, Brownstein MJ: Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus. Nature 357:336–339, 1992 | Article | PubMed | ISI | ChemPort |
  80. Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, Van-Os CH, Van-Oost BA: Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 264:92–95, 1994 | Article | PubMed | ISI | ChemPort |
  81. Nielsen S, Christensen EI, Digiovanni SR, Agre P, Knepper MA: Vasopressin increases AQP-CD water channel expression. (abstract) Eur Kidney Res Forum A2–1, 1994
  82. Howard RL, Bichet DG, Schrier RW: Hypernatremic and polyuric states, in The Kidney. Physiology and Pathophysiology, edited by Seldin DW, Giebisch G, New York, Raven Press, 1992, p 1753
  83. Marples D, Christensen S, Christensen EI, Nielsen S: Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 95:1838–1845, 1995 | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT