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Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors

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Abstract

Mammals rely heavily on olfaction to interact adequately with each other and with their environment1. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant2, trace amine-associated receptor3 and vomeronasal type 1 (ref. 4) or 2 (refs 5–7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.

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Figure 1: FPR genes are expressed by vomeronasal sensory neurons.
Figure 2: Exclusive expression of FPR genes in vomeronasal neurons.
Figure 3: Recognition by FPRs of pathogen/inflammation-related compounds.
Figure 4: Formyl-peptide-evoked Ca 2+ signals in the intact vomeronasal epithelium.

Change history

  • 28 May 2009

    The labels on the x-axis of Fig. 4f were transposed; this has now been corrected.

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Acknowledgements

We thank C.-D. K. Ballif, C. Engelhardt and H. Bartel for technical help, and C. Bauer and P. Descombes for assistance on the NCCR ‘Frontiers in Genetics’ bioimaging and genomic platforms, respectively. We also thank H. Hatt for unlimited access to departmental infrastructure, and P. Vassalli for comments on the manuscript. This work was supported by the Swiss National Science Foundation, the Claraz, Schmidheiny, Volkswagen and Schlumberger Foundations, and the Emmy Noether program of the Deutsche Forschungsgemeinschaft.

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Correspondence to Ivan Rodriguez.

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Supplementary Information

This file contains Supplementary Methods, Supplementary References, Supplementary Figures 1-9 and Supplementary Table 1. (PDF 3884 kb)

Supplementary Movie 1

This movie shows formyl peptide sensitivity in isolated vomeronasal sensory neurons. (MPG 8882 kb)

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Rivière, S., Challet, L., Fluegge, D. et al. Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors. Nature 459, 574–577 (2009). https://doi.org/10.1038/nature08029

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