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Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer

Author

Listed:
  • F. Ango

    (CNRS-UPR 9023, CCIPE)

  • L. Prézeau

    (CNRS-UPR 9023, CCIPE)

  • T. Muller

    (BAYER AG, Pharma Research)

  • J. C. Tu

    (The Johns Hopkins University School of Medicine)

  • B. Xiao

    (The Johns Hopkins University School of Medicine)

  • P. F. Worley

    (The Johns Hopkins University School of Medicine)

  • J. P. Pin

    (CNRS-UPR 9023, CCIPE)

  • J. Bockaert

    (CNRS-UPR 9023, CCIPE)

  • L. Fagni

    (CNRS-UPR 9023, CCIPE)

Abstract

G-protein-coupled receptors (GPCRs) transduce signals from extracellular transmitters to the inside of the cell by activating G proteins. Mutation and overexpression of these receptors have revealed that they can reach their active state even in the absence of agonist, as a result of a natural shift in the equilibrium between their inactive and active conformations1. Such agonist-independent (constitutive) activity has been observed for the glutamate GPCRs (the metabotropic glutamate receptors mGluR1a and mGluR5) when they are overexpressed in heterologous cells2. Here we show that in neurons, the constitutive activity of these receptors is controlled by Homer proteins, which bind directly to the receptors' carboxy-terminal intracellular domains3,4. Disruption of this interaction by mutagenesis or antisense strategies, or expression of endogenous Homer1a (H1a), induces constitutive activity in mGluR1a or mGluR5. Our results show that these glutamate GPCRs can be directly activated by intracellular proteins as well as by agonists.

Suggested Citation

  • F. Ango & L. Prézeau & T. Muller & J. C. Tu & B. Xiao & P. F. Worley & J. P. Pin & J. Bockaert & L. Fagni, 2001. "Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer," Nature, Nature, vol. 411(6840), pages 962-965, June.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6840:d:10.1038_35082096
    DOI: 10.1038/35082096
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