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Open Access

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

  • Klaus Schicker1, 2,
  • Simon Hussl1,
  • Giri K Chandaka1,
  • Kristina Kosenburger1, 2,
  • Jae-Won Yang1,
  • Maria Waldhoer2,
  • Harald H Sitte1 and
  • Stefan Boehm1, 2Email author
BMC Pharmacology20088(Suppl 1):A40

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

Published: 5 November 2008

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.

Declarations

Acknowledgements

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

Authors’ Affiliations

(1)
Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna
(2)
Institute of Experimental and Clinical Pharmacology, Medical University of Graz

Copyright

© Schicker et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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