Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal integration

Marie Laure Rives, Claire Vol, Yugo Fukazawa, Norbert Tinel, Eric Trinquet, Mohammed Akli Ayoub, Ryuichi Shigemoto, Jean Philippe Pin, Laurent Prézeau

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

G protein-coupled receptors (GPCRs) have critical functions in intercellular communication. Although a wide range of different receptors have been identified in the same cells, the mechanism by which signals are integrated remains elusive. The ability of GPCRs to form dimers or larger hetero-oligomers is thought to generate such signal integration. We examined the molecular mechanisms responsible for the GABAB receptor-mediated potentiation of the mGlu receptor signalling reported in Purkinje neurons. We showed that this effect does not require a physical interaction between both receptors. Instead, it is the result of a more general mechanism in which the βγ subunits produced by the Gi-coupled GABAB receptor enhance the mGlu-mediated Gq response. Most importantly, this mechanism could be generally applied to other pairs of Gi- and Gq-coupled receptors and the signal integration varied depending on the time delay between activation of each receptor. Such a mechanism helps explain specific properties of cells expressing two different Gi- and Gq-coupled receptors activated by a single transmitter, or properties of GPCRs naturally coupled to both types of the G protein.

Original languageEnglish
Pages (from-to)2195-2208
Number of pages14
JournalEMBO Journal
Volume28
Issue number15
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Keywords

  • Calcium signalling
  • G protein-coupled receptor
  • Homogenous time-resolved FRET
  • Oligomerization
  • Resonance energy transfer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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