Consequences of point mutations in trout anion exchanger 1 (tAE1) transmembrane domains: evidence that tAE1 can behave as a chloride channel

Journal of Cellular Physiology
Sonia MartialFranck Borgese

Abstract

In this study, we have shown that, when expressed in Xenopus oocytes, trout anion exchanger 1 (tAE1) was able to act as a bifunctional protein, either an anion exchanger or a chloride conductance. Point mutations of tAE1 were carried out and their effect on Cl- conductance and Cl- unidirectional flux were studied. We have shown that mutations made in transmembrane domain 7 had dramatic effects on tAE1 function. Indeed, when these residues were mutated, either individually or together (mutants E632K, D633G, and ED/KG), Cl- conductance was reduced to 28-44% that of wild-type tAE1. Moreover, ion substitution experiments showed that anion selectivity was altered. However, the exchanger function was unchanged, as evidenced by the fact that Cl- influx and K(m) were identical for each of these mutants and similar to the wild-type protein parameters. By contrast, mutations made in the C-terminal domains of the protein (R819M, Q829K) affected both transport functions. Cl- conductance was increased by approximately 200% with respect to tAE1 and anion selectivity was impaired. Likewise, Cl- influx was increased by approximately 260% and was no longer saturable. These and other mutations carried out in transmembrane domains 7, 8, 12-14 of ...Continue Reading

References

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Sep 10, 2005·Biochimica Et Biophysica Acta·Hélène GuizouarnFranck Borgese

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Citations

Jan 25, 2011·The Journal of Biological Chemistry·Damien Barneaud-RoccaHélène Guizouarn
Oct 30, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·David Meredith
Oct 30, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·J C ElloryG W Stewart
Nov 13, 2009·American Journal of Physiology. Cell Physiology·Andrew K StewartSeth L Alper
Aug 31, 2011·International Journal of Cell Biology·Damien Barneaud-RoccaHélène Guizouarn
Feb 24, 2007·The Journal of Physiology·Mark D ParkerMichael J A Tanner
May 24, 2007·Journal of Cellular Physiology·Sonia MartialFranck Borgese
Jun 6, 2008·American Journal of Physiology. Renal Physiology·Stephen WalshHelene Guizouarn
Jul 4, 2012·Molecular Cancer Research : MCR·Michel BidetIsabelle Mus-Veteau
Mar 11, 2008·Blood Cells, Molecules & Diseases·Seth L AlperCarlo Brugnara

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