Activation state of the M3 muscarinic acetylcholine receptor modulates mammalian odorant receptor signaling.

Journal Article (Journal Article)

A diverse repertoire of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) enables cells to sense their environment. Mammalian olfaction requires the activation of odorant receptors (ORs), the largest family of GPCRs; however, whether ORs functionally interact with other families of GPCRs is unclear. We show that the interaction of ORs with the type 3 muscarinic acetylcholine receptor (M3-R), which is found in olfactory sensory neurons (OSNs), modulated OR responses to cognate odorants. In human embryonic kidney-293T cells, ORs and the M3-R physically interacted, and the M3-R increased the potency and efficacy of odorant-elicited responses of several ORs. Selective M3-R antagonists attenuated odorant-dependent activation of OSNs, and, when the M3-R and ORs were expressed in transfected cells, OR activation was enhanced by muscarinic agonists and inhibited by muscarinic antagonists. Furthermore, M3-R-dependent potentiation of OR signaling synergized with that of receptor transporting protein 1S (RTP1S), an accessory factor required for the efficient membrane targeting of ORs. However, the M3-R did not enhance the abundance of ORs at the cell surface, suggesting that the M3-R acted through a distinct mechanism independent of RTP1S. Finally, the activation of ORs by cognate odorants transactivated the M3-R in the absence of its agonist. The crosstalk between ORs and the M3-R suggests that the functional coupling of ORs and the M3-R is required for robust OR activation.

Full Text

Duke Authors

Cited Authors

  • Li, YR; Matsunami, H

Published Date

  • January 11, 2011

Published In

Volume / Issue

  • 4 / 155

Start / End Page

  • ra1 -

PubMed ID

  • 21224444

Pubmed Central ID

  • PMC3034603

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2001230


  • eng

Conference Location

  • United States