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

J Cell Physiol. 2006 Jun;207(3):829-35. doi: 10.1002/jcp.20631.


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 tAE1 allow us to demonstrate without doubt that, in addition to its anion exchanger activity, tAE1 can also function as a chloride channel. Above all, this work led us to identify amino acids involved in this double function organization.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anion Exchange Protein 1, Erythrocyte / chemistry
  • Anion Exchange Protein 1, Erythrocyte / genetics
  • Anion Exchange Protein 1, Erythrocyte / metabolism*
  • Cell Membrane / genetics*
  • Cell Membrane / metabolism*
  • Chloride Channels / chemistry
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorine / chemistry
  • Chlorine / metabolism
  • Electrophysiology
  • Humans
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Point Mutation / genetics
  • Sequence Alignment
  • Trout / genetics*
  • Trout / metabolism*
  • Xenopus laevis


  • Anion Exchange Protein 1, Erythrocyte
  • Chloride Channels
  • Chlorine