Muscarinic acetylcholine receptor M3 modulates odorant receptor activity via inhibition of β-arrestin-2 recruitment

Yue Jiang, Yun Rose Li, Huikai Tian, Minghong Ma () and Hiroaki Matsunami ()
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Yue Jiang: Duke University Medical Center
Yun Rose Li: Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine
Huikai Tian: University of Pennsylvania School of Medicine
Minghong Ma: Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine
Hiroaki Matsunami: Duke University Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract The olfactory system in rodents serves a critical function in social, reproductive and survival behaviours. Processing of chemosensory signals in the brain is dynamically regulated in part by an animal’s physiological state. We previously reported that type 3 muscarinic acetylcholine receptors (M3-Rs) physically interact with odorant receptors (ORs) to promote odour-induced responses in a heterologous expression system. However, it is not known how M3-Rs affect the ability of olfactory sensory neurons (OSNs) to respond to odours. Here, we show that an M3-R antagonist attenuates odour-induced responses in OSNs from wild-type, but not M3-R-null, mice. Using a novel molecular assay, we demonstrate that the activation of M3-Rs inhibits the recruitment of β-arrestin-2 to ORs, resulting in a potentiation of odour-induced responses in OSNs. These results suggest a role for acetylcholine in modulating olfactory processing at the initial stages of signal transduction in the olfactory system.

Date: 2015
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DOI: 10.1038/ncomms7448

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