Letter

Nature 459, 574-577 (28 May 2009) | doi:10.1038/nature08029; Received 14 November 2008; Accepted 2 April 2009; Published online 22 April 2009; Corrected 28 May 2009

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

Stéphane Rivière1,3, Ludivine Challet1,3, Daniela Fluegge2,3,4, Marc Spehr2,4 & Ivan Rodriguez1

  1. Department of Zoology and Animal Biology, and National Center of Competence 'Frontiers in Genetics', University of Geneva, 1205 Geneva, Switzerland
  2. Department of Cellular Physiology, Ruhr University, 44780 Bochum, Germany
  3. These authors contributed equally to this work.
  4. Present address: Department of Chemosensation, Institute of Biology II, RWTH Aachen University, 52074 Aachen, Germany.

Correspondence to: Ivan Rodriguez1 Correspondence and requests for materials should be addressed to I.R. (Email: ivan.rodriguez@unige.ch).

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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