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P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties.

Abstract

Ligand-gated ion channels are prototypic oligomeric membrane proteins whose stoichiometry determines their functional properties and subcellular localization. Deciphering the quaternary structure of such protein complexes is an arduous task and usually requires the combination of multiple approaches. ATP-gated P2X receptors are formed by the association of three subunits, but the quaternary arrangement of the seven P2X subunits at the plasma membrane remains poorly characterized. By combining bioluminescence resonance energy transfer, bifunctional fluorescence complementation and protein biochemistry, we developed an experimental approach that allows precise determination of rat P2X receptor quaternary assembly. We found that P2X5 subunits associate with P2X1, P2X2, and P2X4 subunits. We demonstrate that P2X5 and P2X2 subunits interact to form as yet uncharacterized heteromeric receptors with alternate stoichiometries, both present at the plasma membrane. P2X2/5 receptors display functional properties such as pore dilatation, membrane blebbing, and phosphatidylserine exposure that were previously thought to be characteristic hallmarks of the P2X7 receptor. In mouse, P2X2 and P2X5 subunits colocalize and physically interact in specific neuronal populations suggesting that other P2X receptors might contribute to cellular responses typically attributed to P2X7 receptor.

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  • Publisher Full Text
  • Authors

    Compan V, Ulmann L, Stelmashenko O, Chemin J, Chaumont S, Rassendren F

    Institution

    Universités de Montpellier, Montpellier, France.

    Source

    The Journal of neuroscience : the official journal of the Society for Neuroscience 32:12 2012 Mar 21 pg 4284-96

    MeSH

    Adenosine Triphosphate
    Animals
    Annexin A5
    Benzoxazoles
    Bioluminescence Resonance Energy Transfer Techniques
    Brain
    Enzyme-Linked Immunosorbent Assay
    Ganglia, Spinal
    HEK293 Cells
    Humans
    Immunoprecipitation
    Luminescent Proteins
    Membrane Potentials
    Mice
    Mutagenesis, Site-Directed
    Mutation
    Patch-Clamp Techniques
    Protein Subunits
    Purinergic Agents
    Quinolinium Compounds
    Receptors, Purinergic P2X2
    Receptors, Purinergic P2X5
    Receptors, Purinergic P2X7
    Transfection
    Video Recording
    Xenopus laevis

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22442090