Aquaporin 4 as a NH3 Channel.
| Autor: | Assentoft M; From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark., Kaptan S; Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany, and., Schneider HP; Division of General Zoology, Department of Biology, University of Kaiserslautern, 67653 Kaiserslautern, Germany., Deitmer JW; Division of General Zoology, Department of Biology, University of Kaiserslautern, 67653 Kaiserslautern, Germany., de Groot BL; Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany, and., MacAulay N; From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark, macaulay@sund.ku.dk. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2016 Sep 02; Vol. 291 (36), pp. 19184-95. Date of Electronic Publication: 2016 Jul 19. |
| DOI: | 10.1074/jbc.M116.740217 |
| Abstrakt: | Ammonia is a biologically potent molecule, and the regulation of ammonia levels in the mammalian body is, therefore, strictly controlled. The molecular paths of ammonia permeation across plasma membranes remain ill-defined, but the structural similarity of water and NH3 has pointed to the aquaporins as putative NH3-permeable pores. Accordingly, a range of aquaporins from mammals, plants, fungi, and protozoans demonstrates ammonia permeability. Aquaporin 4 (AQP4) is highly expressed at perivascular glia end-feet in the mammalian brain and may, with this prominent localization at the blood-brain-interface, participate in the exchange of ammonia, which is required to sustain the glutamate-glutamine cycle. Here we observe that AQP4-expressing Xenopus oocytes display a reflection coefficient <1 for NH4Cl at pH 8.0, at which pH an increased amount of the ammonia occurs in the form of NH3 Taken together with an NH4Cl-mediated intracellular alkalization (or lesser acidification) of AQP4-expressing oocytes, these data suggest that NH3 is able to permeate the pore of AQP4. Exposure to NH4Cl increased the membrane currents to a similar extent in uninjected oocytes and in oocytes expressing AQP4, indicating that the ionic NH4 (+) did not permeate AQP4. Molecular dynamics simulations revealed partial pore permeation events of NH3 but not of NH4 (+) and a reduced energy barrier for NH3 permeation through AQP4 compared with that of a cholesterol-containing lipid bilayer, suggesting AQP4 as a favored transmembrane route for NH3 Our data propose that AQP4 belongs to the growing list of NH3-permeable water channels. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.) |
| Databáze: | MEDLINE |
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