A natural dominant negative P2x1 receptor due to deletion of a single amino acid residue

Cecile Oury, Emese Toth-Zsamboki, Chris Van Geet, Chantal Thys, Lin Wei, Bernd Nilius, Jos Vermylen, Marc F. Hoylaerts

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Abstract

The P2X1 receptor belongs to a family of oligomeric ATP-gated ion channels with intracellular N and C termini and two transmembrane segments separating a large extracellular domain. Here, we describe a naturally occurring dominant negative P2X1 mutant. This mutant lacks one leucine within a stretch of four leucine residues in its second transmembrane domain (TM2) (amino acids 351-354). Confocal microscopy revealed proper plasma membrane localization of the mutant in stably transfected HEK293 cells. Nevertheless, voltage-clamped HEK293 cells expressing mutated P2X1 channels failed to develop an ATP or ADP-induced current. Furthermore, when co-expressed with the wild type receptor in Xenopus oocytes, the mutated protein exhibited a dose-dependent dominant negative effect on the normal ATP or ADP-induced P2X1 channel activity. These data indicate that deletion of a single apolar amino acid residue at the inner border of the P2X1 TM2 generates a nonfunctional channel. The inactive and dominant negative form of the P2X1 receptor may constitute a new tool for the study of the physiological role of this channel in native cells.

Original languageEnglish
Pages (from-to)22611-22614
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number30
DOIs
Publication statusPublished - Jul 28 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oury, C., Toth-Zsamboki, E., Van Geet, C., Thys, C., Wei, L., Nilius, B., Vermylen, J., & Hoylaerts, M. F. (2000). A natural dominant negative P2x1 receptor due to deletion of a single amino acid residue. Journal of Biological Chemistry, 275(30), 22611-22614. https://doi.org/10.1074/jbc.C000305200