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A membrane network of receptors and enzymes for adenine nucleotides and nucleosides

Most cells express more than one receptor plus degrading enzymes for adenine nucleotides or nucleosides, and cellular responses to purines are rarely compatible with the actions of single receptors. Therefore, these receptors are viewed as components of a combinatorial receptor web rather than self-dependent entities, but it remained unclear to what extent they can associate with each other to form signalling units. P2Y1, P2Y2, P2Y12, P2Y13, P2X2, A1, A2A receptors and NTPDase1 and -2 were expressed as fluorescent fusion proteins which were targeted to membranes and signalled like the unlabelled counterparts. When tested by FRET microscopy, all the G protein-coupled receptors proved able to form heterooligomers with each other, and P2Y1, P2Y13, A1, A2A, and P2X2 receptors also formed homooligomers. P2Y receptors did not associate with P2X, but G protein-coupled receptors formed heterooligomers with NTPDase1, but not with NTPDase2. The specificity of prototypic interactions (P2Y1/P2Y1, A2A/P2Y1, A2A/P2Y12) was corroborated by FRET competition or co-immunoprecipitation. These results demonstrate that G protein-coupled purine receptors associate with each other and with NTPDase1 in a highly promiscuous manner. Thus, purinergic signalling is not only determined by the expression of receptors and enzymes but also by their direct interaction within a previously unrecognized multifarious membrane network.

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Supported by the Austrian Science Fund FWF (P17611 and W1205).

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Correspondence to Stefan Boehm.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Schicker, K., Hussl, S., Chandaka, G.K. et al. A membrane network of receptors and enzymes for adenine nucleotides and nucleosides. BMC Pharmacol 8 (Suppl 1), A40 (2008). https://doi.org/10.1186/1471-2210-8-S1-A40

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  • DOI: https://doi.org/10.1186/1471-2210-8-S1-A40

Keywords

  • Purine
  • Nucleoside
  • P2X2 Receptor
  • Adenine Nucleotide
  • Purinergic Signalling