Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-25T19:15:28.790Z Has data issue: false hasContentIssue false
  • English
  • Français

Mammalian aquaporins: diverse physiological roles and potential clinical significance

Published online by Cambridge University Press:  16 May 2008

A. S. Verkman
A. S. Verkman
Affiliation:
Departments of Medicine and Physiology, Cardiovascular Research Institute, 1246 Health Sciences East Tower, University of California, San Francisco, CA 94143-0521, USA. Tel: +1 415 476 8530; Fax: +1 415-665-3847; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Aquaporins have multiple distinct roles in mammalian physiology. Phenotype analysis of aquaporin-knockout mice has confirmed the predicted role of aquaporins in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Aquaporins also facilitate water movement into and out of the brain in various pathologies such as stroke, tumour, infection and hydrocephalus. A major, unexpected cellular role of aquaporins was revealed by analysis of knockout mice: aquaporins facilitate cell migration, as occurs in angiogenesis, tumour metastasis, wound healing, and glial scar formation. Another unexpected role of aquaporins is in neural function – in sensory signalling and seizure activity. The water-transporting function of aquaporins is likely responsible for these roles. A subset of aquaporins that transport both water and glycerol, the ‘aquaglyceroporins’, regulate glycerol content in epidermal, fat and other tissues. Mice lacking various aquaglyceroporins have several interesting phenotypes, including dry skin, resistance to skin carcinogenesis, impaired cell proliferation, and altered fat metabolism. The various roles of aquaporins might be exploited clinically by development of drugs to alter aquaporin expression or function, which could serve as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e13
Copyright
Copyright ©Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Gonen, T. and Walz, T. (2006) The structure of aquaporins. Q Rev Biophys 39, 361-396CrossRefGoogle ScholarPubMed
2Fujiyoshi, Y. et al. (2002) Structure and function of water channels. Curr Opin Struct Biol 12, 509-515CrossRefGoogle ScholarPubMed
3Hub, J.S. and de Groot, B.L. (2008) Mechanism of selectivity of aquaporins and aquaglyceroporins. Proc Natl Acad Sci U S A 105, 1198-1203CrossRefGoogle ScholarPubMed
4Deen, P.M. et al. (1994) Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 264, 92-95CrossRefGoogle ScholarPubMed
5Verkman, A.S. (2007) Role of aquaporins in lung fluid physiology. Resp Physiol Neurobiol 159, 324-330CrossRefGoogle Scholar
6Verkman, A.S. and Thiagarajah, J.R. (2006) Physiology of water transport in the gastrointestinal tract. In Physiology of the Gastrointestinal Tract (Vol. 4) Johnson, L.R. et al. , eds), New York, Academic Press, pp. 1827-1845Google Scholar
7Yang, B. et al. (2000) Skeletal muscle function and water permeability in aquaporin-4 deficient mice. Am J Physiol 278, C1108-1115CrossRefGoogle ScholarPubMed
8Song, Y., Sonawane, N. and Verkman, A.S. (2002) Localization of aquaporin-5 in sweat glands and functional analysis using knockout mice. J Physiol 541, 561-568CrossRefGoogle ScholarPubMed
9Yang, B. et al. (2005) Phenotype analysis of aquaporin-8 null mice. Am J Physiol 288, C1161-C1170CrossRefGoogle ScholarPubMed
10Holm, L.M. et al. (2005) NH3 and NH4+ permeability in aquaporin-expressing Xenopus oocytes. Pflugers Arch 450, 415-248CrossRefGoogle ScholarPubMed
11Cooper, G.J. and Boron, W.F. (1998) Effect of PCMBS on CO2 permeability of Xenopus oocytes expressing aquaporin 1 or its C189S mutant. Am J Physiol 275, C1481-1486CrossRefGoogle ScholarPubMed
12Yang, B. et al. (2000) Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes. J Biol Chem 275, 2686-2692CrossRefGoogle ScholarPubMed
13Fang, X. et al. (2002) Evidence against aquaporin dependent CO2 permeability in lung and kidney. J Physiol (London) 543, 63-69CrossRefGoogle Scholar
14Yang, B. et al. (2006) Evidence from knockout mice against physiologically significant aquaporin-8 facilitated ammonia transport. Am J Physiol 291, C417-C423CrossRefGoogle ScholarPubMed
15Yang, B., Zhao, D. and Verkman, A.S. (2006) Evidence against functionally significant aquaporin expression in mitochondria. J Biol Chem 281, 16202-16206CrossRefGoogle ScholarPubMed
16Zhang, H. and Verkman, A.S. (2008) Aquaporin-4 independent Kir4.1 K+ channel function in brain glial cells. Mol Cell Neurosci 37, 3-10CrossRefGoogle ScholarPubMed
17Ruiz-Ederra, J., Zhang, H. and Verkman, A.S. (2007) Evidence against functional interaction between aquaporin-4 water channels and Kir4.1 K+ channels in retinal Müller cells. J Biol Chem 282, 21866-21872CrossRefGoogle ScholarPubMed
18Ma, T. et al. (1999) Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. J Biol Chem 274, 20071-20074CrossRefGoogle ScholarPubMed
19Krane, C.M. et al. (2001) Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem 27, 23413-23420CrossRefGoogle Scholar
20Song, Y. and Verkman, A.S. (2001) Aquaporin-5 dependent fluid secretion in airway submucosal glands. J Biol Chem 276, 41288-41292CrossRefGoogle ScholarPubMed
21Oshio, K. et al. (2005) Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel aquaporin-1. FASEB J 19, 76-78CrossRefGoogle ScholarPubMed
22Zhang, D., Vetrivel, L. and Verkman, A.S. (2002) Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. J Gen Physiol 119, 561-569CrossRefGoogle ScholarPubMed
23Schnermann, J. et al. (1998) Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice. Proc Natl Acad Sci U S A 95, 9660-9664CrossRefGoogle ScholarPubMed
24Vallon, V., Verkman, A.S. and Schnermann, J. (2000) Luminal hypotonicity in proximal tubules of aquaporin-1 knockout mice. Am J Physiol 278, F1030-F1033Google ScholarPubMed
25Bai, C. et al. (1999) Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. J Clin Invest 103, 555-561CrossRefGoogle ScholarPubMed
26Ma, T. et al. (2000) Lung fluid transport in aquaporin-5 knockout mice. J Clin Invest 105, 93-100CrossRefGoogle ScholarPubMed
27Song, Y. et al. (2000) Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in edema formation following acute lung injury, studies in transgenic aquaporin null mice. J Physiol 525, 771-779CrossRefGoogle ScholarPubMed
28Song, Y. et al. (2001) Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration. J Gen Physiol 117, 573-582CrossRefGoogle ScholarPubMed
29Yang, B. et al. (1999) Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice. Am J Physiol 276, C76-81CrossRefGoogle ScholarPubMed
30Song, Y. et al. (2000) Role of aquaporin water channels in pleural fluid dynamics. Am J Physiol 279, C1744-1750CrossRefGoogle ScholarPubMed
31Ma, T. et al. (1998) Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 273, 4296-4299CrossRefGoogle ScholarPubMed
32Ma, T. et al. (2000) Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc Natl Acad Sci U S A 97, 4386-4391CrossRefGoogle ScholarPubMed
33Ma, T. et al. (1997) Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. J Clin Invest 100, 957-962CrossRefGoogle ScholarPubMed
34Chou, C.L. et al. (1999) Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice. J Clin Invest 103, 491-496CrossRefGoogle ScholarPubMed
35Pallone, T.L. et al. (2000) Requirement of aquaporin-1 for NaCl-driven water transport across descending vasa recta. J Clin Invest 105, 215-222CrossRefGoogle ScholarPubMed
36Sohara, E. et al. (2005) Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice. Am J Physiol 289, F1195-F1200Google ScholarPubMed
37Chou, C.L. et al. (1998) Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice. Am J Physiol 274, C549-554CrossRefGoogle ScholarPubMed
38Verkman, A.S.Dissecting the role of aquaporins in renal pathophysiology using transgenic mice. Semin Nephrol (in press)Google Scholar
39Solenov, E. et al. (2004) Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method. Am J Physiol 286, C426-432CrossRefGoogle ScholarPubMed
40Thiagarajah, J.R., Papadopoulos, M.C. and Verkman, A.S. (2005) Non-invasive early detection of brain edema in mice by near-infrared light scattering. J Neurosci Res 80, 293-299CrossRefGoogle Scholar
41Papadopoulos, M.C. and Verkman, A.S. (2005) Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem 280, 13906-13912CrossRefGoogle ScholarPubMed
42Klatzo, I. (1994) Evolution of brain edema concepts. Acta Neurochir Suppl (Wien) 60, 3-6Google ScholarPubMed
43Manley, G.T. et al. (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nature Med 6, 159-163CrossRefGoogle ScholarPubMed
44Amiry-Moghaddam, M. et al. (2003) An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci U S A 100, 2106-2111CrossRefGoogle ScholarPubMed
45Saadoun, S. et al. Greatly improved neurological outcome in AQP4-deficient mice after spinal cord compression injury. Brain 131, 1087-1098CrossRefGoogle Scholar
46Papadopoulos, M.C. et al. (2004) Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 18, 1291-1293CrossRefGoogle ScholarPubMed
47Bloch, O. et al. (2005) Aquaporin-4 gene deletion in mice increases focal edema associated with brain abscess. J Neurochem 95, 254-262CrossRefGoogle ScholarPubMed
48Bloch, O., Manley, G.T. and Verkman, A.S. (2006) Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4 deficient mice. J Cereb Blood Flow Metab 26, 1527-1537CrossRefGoogle ScholarPubMed
49Berry, V. et al. (2000) Missense mutations in MIP underlie autosomal dominant ‘polymorphic’ and lamellar cataracts linked to 12q. Nat Genet 25, 15-17CrossRefGoogle ScholarPubMed
50Ruiz-Ederra, J. and Verkman, A.S. (2006) Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1deficient mice. Invest Opthalmol Vis Sci 47, 3960-3967CrossRefGoogle ScholarPubMed
51Thiagarajah, J.R. and Verkman, A.S. (2002) Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling. J Biol Chem 277, 19139-19144CrossRefGoogle ScholarPubMed
52Li, J., Patil, R.V. and Verkman, A.S. (2002) Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels. Invest Ophthalmol Vis Sci 43, 573-579Google ScholarPubMed
53Levin, M.H. and Verkman, A.S. (2004) Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfluorimetric measurements in cornea and conjunctiva. Invest Ophthalmol Vis Sci 45, 4423-4432CrossRefGoogle ScholarPubMed
54Da, T. and Verkman, A.S. (2004) Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci 45, 4477-4483CrossRefGoogle ScholarPubMed
55Endo, M. et al. (1999) Water channel (aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res 58, 89-98CrossRefGoogle ScholarPubMed
56Saadoun, S. et al. (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434, 786-792CrossRefGoogle ScholarPubMed
57Saadoun, S. et al. (2005) Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci 118, 5691-5698CrossRefGoogle ScholarPubMed
58Auguste, K.I. et al. (2007) Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury FASEB J 21, 108-116CrossRefGoogle Scholar
59Levin, M.H. and Verkman, A.S. (2006) Aquaporin-3-dependent cell migration and proliferation during corneal re-epithelialization. Invest Ophthalmol Vis Sci 47, 4365-4372CrossRefGoogle ScholarPubMed
60Hara-Chikuma, M. and Verkman, A.S. (2008) Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med 86, 221-231CrossRefGoogle ScholarPubMed
61Hara-Chikuma, M. and Verkman, A.S. (2006) Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule. J Am Soc Nephrol 17, 39-45CrossRefGoogle ScholarPubMed
62Hu, J. and Verkman, A.S. (2006) Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. Faseb J 20, 1892-1894CrossRefGoogle ScholarPubMed
63Condeelis, J. (1993) Life at the leading edge: the formation of cell protrusions. Annu Rev Cell Biol 9, 411-444CrossRefGoogle Scholar
64Charras, G.T. et al. (2005) Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435, 365-369CrossRefGoogle ScholarPubMed
65Li, J. and Verkman, A.S. (2001) Impaired hearing in mice lacking aquaporin-4 water channels. J Biol Chem 276, 31233-31237CrossRefGoogle ScholarPubMed
66Mhatre, A.N. et al. (2002) Aquaporin 4 expression in the mammalian inner ear and its role in hearing. Biochem Biophys Res Commun 297, 987-996CrossRefGoogle ScholarPubMed
67Binder, D.K. et al. (2004) Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport 15, 259-262CrossRefGoogle ScholarPubMed
68Binder, D.K. et al. (2006) Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels. Glia 53, 631-636CrossRefGoogle ScholarPubMed
69Amiry-Moghaddam, M. et al. (2003) Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice. Proc Natl Acad Sci U S A 100, 13615-13620CrossRefGoogle ScholarPubMed
70Lu, D. et al. (2008) Impaired olfaction in mice lacking aquaporin-4 water channels. FASEB J (in press)Google ScholarPubMed
71Padmawar, P., Yao, X., Bloch, O. et al. (2005) K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator. Nat Methods 2, 825-827CrossRefGoogle ScholarPubMed
72Binder, D.K. et al. (2004) In vivo measurement of brain extracellular space diffusion by cortical surface photobleaching. J Neurosci 24, 8049-8056CrossRefGoogle ScholarPubMed
73Zador, Z. et al. Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain. FASEB J 22, 870-879CrossRefGoogle Scholar
74Rojek, A.M. et al. (2007) Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci U S A 104, 3609-3614CrossRefGoogle ScholarPubMed
75Ma, T. et al. (2002) Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. J Biol Chem 277, 17147-17153CrossRefGoogle ScholarPubMed
76Hara, M., Ma, T. and Verkman, A.S. (2002) Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery. J Biol Chem 277, 46616-46621CrossRefGoogle ScholarPubMed
77Hara, M. and Verkman, A.S. (2003) Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci U S A 100, 7360-7365CrossRefGoogle ScholarPubMed
78Hara-Chikuma, M. and Verkman, A.S. (2008) Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol 28, 326-332CrossRefGoogle ScholarPubMed
79Thiagarajah, J.R., Zhao, D. and Verkman, A.S. (2007) Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut 56, 1529-1535CrossRefGoogle ScholarPubMed
80Verkman, A.S.A cautionary note on cosmetics containing ingredients that increase aquaporin-3 expression. Exp Dermatol (in press)Google Scholar
81Hara-Chikuma, M. et al. (2005) Progressive adipocyte hypertrophy in aquaporin-7 deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 28, 15493-15496CrossRefGoogle Scholar
82Hibuse, T. et al. (2005) Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci U S A 102, 10993-10998CrossRefGoogle ScholarPubMed
83Funahashi, T. et al. (2006) Impact of glycerol gateway molecule in adipocytes. Cell Mol Biol (Noisy-le-grand) 52, 40-45Google ScholarPubMed
84Lennon, V.A. et al. (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202, 473-477CrossRefGoogle Scholar
85Rai, T. et al. (1997) Urinary excretion of aquaporin-2 water channel protein in human and rat. J Am Soc Nephrol 8, 1357-1362CrossRefGoogle ScholarPubMed
86Kwon, T.H. et al. (2001) Physiology and pathophysiology of renal aquaporins. Semin Nephrol 21, 231-238CrossRefGoogle ScholarPubMed
87Hara-Chikuma, M. and Verkman, A.S.Roles of aquaporin-3 in epidermis. J Invest Dermatol (in press)Google Scholar
88Lee, T.S. et al. (2004) Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy. Acta Neuropathol 108, 493-502CrossRefGoogle ScholarPubMed
89Ceperuelo-Mallafré, V. et al. (2007) Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes. J Clin Endocrinol Metab 92, 3640-3645CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

General information on aquaporins:

http://www.ucsf.edu/verklabGoogle Scholar
http://www.ks.uiuc.edu/Research/aquaporins/Google Scholar
http://en.wikipedia.org/wiki/AquaporinGoogle Scholar
http://www.congre.co.jp/aqp2007/Google Scholar
http://www.scanbalt.org/sw14185.aspGoogle Scholar
http://www.ndif.orgGoogle Scholar