Rapid gating and anion permeability of an intracellular aquaporin

ABSTRACT Aquaporin (AQP) water-channel proteins are freely permeated by water but not by ions or charged solutes1. Although mammalian aquaporins were believed to be located in plasma

membranes, rat AQP6 is restricted to intracellular vesicles in renal epithelia2. Here we show that AQP6 is functionally distinct from other known aquaporins. When expressed in _Xenopus

laevis_ oocytes, AQP6 exhibits low basal water permeability; however, when treated with the known water channel inhibitor, Hg2+, the water permeability of AQP6 oocytes rapidly rises up to

tenfold and is accompanied by ion conductance. AQP6 colocalizes with H+-ATPase in intracellular vesicles of acid-secreting α-intercalated cells in renal collecting duct. At pH less than 5.5,

anion conductance is rapidly and reversibly activated in AQP6 oocytes. Site-directed mutation of lysine to glutamate at position 72 in the cytoplasmic mouth of the pore changes the

cation/anion selectivity, but leaves low pH activation intact. Our results demonstrate unusual biophysical properties of an aquaporin, and indicate that anion-channel function may now be

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AQP6 plasmid, M. A. Knepper for the anti-H+-ATPase, and M. R. T. Hall for confocal microscopy. Support was provided by grants from the NIH and the Cystic Fibrosis Foundation (P.A. and

W.B.G.), the Human Frontier Science Program (M.Y.), and the Novo Nordic Foundation, the Karen Elise Jensen Foundation, the Danish Medical Research Council, the Biomembrane Research Center at

Unviersity of Aarhus and the EU Commission (EU-Biotech and TMR Programmes) (S.N.). AUTHOR INFORMATION Author notes * Masato Yasui, Akihiro Hazama, Tae-Hwan Kwon and Søren Nielsen: These

authors contributed equally to this work AUTHORS AND AFFILIATIONS * Departments of Biological Chemistry, Medicine, Johns Hopkins University School of Medicine, MD 21205, Baltimore, USA

Masato Yasui & Peter Agre * Physiology, Johns Hopkins University School of Medicine, MD 21205, Baltimore, USA Akihiro Hazama & Wm. B. Guggino * Department of Cell Biology, Institute

of Anatomy, University of Aarhus, DK-8000, Denmark Tae-Hwan Kwon & Søren Nielsen Authors * Masato Yasui View author publications You can also search for this author inPubMed Google

Scholar * Akihiro Hazama View author publications You can also search for this author inPubMed Google Scholar * Tae-Hwan Kwon View author publications You can also search for this author

inPubMed Google Scholar * Søren Nielsen View author publications You can also search for this author inPubMed Google Scholar * Wm. B. Guggino View author publications You can also search for

this author inPubMed Google Scholar * Peter Agre View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Peter Agre.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yasui, M., Hazama, A., Kwon, TH. _et al._ Rapid gating and anion permeability of an intracellular

aquaporin. _Nature_ 402, 184–187 (1999). https://doi.org/10.1038/46045 Download citation * Received: 28 July 1999 * Accepted: 21 September 1999 * Issue Date: 11 November 1999 * DOI:

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