Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors (original) (raw)

Nature volume 459, pages 574–577 (2009)Cite this article

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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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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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Author notes

  1. Daniela Fluegge & Marc Spehr
    Present address: Present address: Department of Chemosensation, Institute of Biology II, RWTH Aachen University, 52074 Aachen, Germany.,
  2. Stéphane Rivière, Ludivine Challet and Daniela Fluegge: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Zoology and Animal Biology, and National Center of Competence ‘Frontiers in Genetics’, University of Geneva, 1205 Geneva, Switzerland
    Stéphane Rivière, Ludivine Challet & Ivan Rodriguez
  2. Department of Cellular Physiology, Ruhr University, 44780 Bochum, Germany
    Daniela Fluegge & Marc Spehr

Authors

  1. Stéphane Rivière
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  2. Ludivine Challet
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  3. Daniela Fluegge
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  4. Marc Spehr
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  5. Ivan Rodriguez
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Corresponding author

Correspondence toIvan Rodriguez.

Supplementary information

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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Editorial Summary

A new chemosensor family

To date, four types of olfactory receptors have been described in mammals — odorant receptors, trace amine-associated receptors and vomeronasal type 1 and type 2 receptor superfamilies. Rivière et al. now report the identification of a additional novel olfactory receptor family, expressed by mouse vomeronasal sensory neurons. This family is encoded by five members of the formyl peptide receptor-related gene family (FPRs), which are otherwise known to mediate immune cell response to infection Cells expressing FPRs respond to ligands associated with disease and inflammation, which are excreted in urine, raising the possibility that FPRs detect the health status of individuals.

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