Molecular Characterization of a Broad Selectivity Neutral Solute Channel*
- Hiroyasu Tsukaguchi‡,
- Chairat Shayakul§,
- Urs V. Berger,
- Bryan Mackenzie¶,
- Sreenivas Devidas‖,
- William B. Guggino‖,
- Alfred N. van Hoek**‡ and
- Matthias A. Hediger§§
- From the Renal Division, Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, the‖Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and the **Renal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129
Abstract
In all living cells, coordination of solute and water movement across cell membranes is of critical importance for osmotic balance. The current concept is that these processes are of distinct biophysical nature. Here we report the expression cloning of a liver cDNA encoding a unique promiscuous solute channel (AQP9) that confers high permeability for both solutes and water. AQP9 mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl−, and deprotonated monocarboxylates are excluded. The properties of AQP9 define a new evolutionary branch of the major intrinsic protein family of aquaporin proteins and describe a previously unknown mechanism by which a large variety of solutes and water can pass through a single pore, enabling rapid cellular uptake or exit of metabolites with minimal osmotic perturbation.
Footnotes
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↵* This work was supported in part by National Institutes of Health Grants DK46289 (to M. A. H.) and DK32753 (to W. B. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF016406.
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↵‡ Supported by a Research Fellowship of the National Kidney Foundation.
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↵§ Supported by the Siriraj-China Medical Board, Mahidol University, Thailand.
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↵¶ Samuel A. Levine Fellow of the American Heart Association, Massachusetts Affiliate.
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↵‡ Supported by National Institutes of Health Grant DK38452 (to Dr. Dennis Brown).
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↵§§ To whom correspondence should be addressed: Renal Division, Brigham & Women’s Hospital, 77 Ave. Louis Pasteur, Boston MA 02115. Tel.: 617-525-5820; Fax: 617-525-5830; E-mail:mhediger{at}rics.bwh.harvard.edu.
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↵2 H. Tsukaguchi and M. A. Hediger, unpublished data.
- Abbreviations:
- AQP
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aquaporin
- UT
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urea transporter
- kb
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kilobase pairs.
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- Received April 22, 1998.
- Revision received June 15, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
