The Vomeronasal Organ Mediates Interspecies Defensive Behaviors through Detection of Protein Pheromone Homologs

Abstract

Summary Potential predators emit uncharacterized chemosignals that warn receiving species of danger. Neurons that sense these stimuli remain unknown. Here we show that detection and processing of fear-evoking odors emitted from cat, rat, and snake require the function of sensory neurons in the vomeronasal organ. To investigate the molecular nature of the sensory cues emitted by predators, we isolated the salient ligands from two species using a combination of innate behavioral assays in naïve receiving animals, calcium imaging, and cFos induction. Surprisingly, the defensive behavior-promoting activity released by other animals is encoded by species-specific ligands belonging to the major urinary protein (Mup) family, homologs of aggression-promoting mouse pheromones. We show that recombinant Mup proteins are sufficient to activate sensory neurons and initiate defensive behavior similar to native odors. This co-option of existing sensory mechanisms provides a molecular solution to the difficult problem of evolving a variety of species-specific molecular detectors.

Mouse alarm pheromone shares structural similarity with predator scents

“…Here, we show that the class of volatile heterocyclic sulfur-or nitrogen-containing compounds generated by meat digestion is specifically recognized by the neurons of the Grueneberg ganglion. This result supports previously published observations reporting that TMT detection still occurred in mice where the main VNO-signaling element, the transient receptor potential channels type 2 (TRPC2) (44), or the key MOE canonical component, the cyclic nucleotide-gated channels A2 (CNGA2) (52), have been genetically deleted. Moreover, TMT detection was also reported to be unaffected by a zinc sulfate treatment inducing a transient anosmia (53).…”

“…The volatile 2-phenylethylamine, a component of carnivore urine, is, for example, recognized in the mouse by the trace amine-associated receptor TAAR4 expressed in the neurons of the MOE (45). On the other hand, the nonvolatile major urinary protein family from predators is recognized by the neurons of the VNO (44). Here, we show that the class of volatile heterocyclic sulfur-or nitrogen-containing compounds generated by meat digestion is specifically recognized by the neurons of the Grueneberg ganglion.…”

“…Interestingly, SBT shares its chemical structure with a different class of odorant molecules also involved in danger communication: the molecules found in rodent predator scents (44)(45)(46) (Fig. 2 C and H).…”

α2u-globulins mediate manipulation of host attractiveness in Toxoplasma gondii–Rattus novergicus association

“…Subsequently, female preference for low-and high-molecular weight fractions of the urine was separately quantified (LMW and HMW, respectively; cutoff = 3 kDa). Volatiles bound to HMW fraction were displaced by a competitive molecule, menadione (Papes et al, 2010). Volatiles in HMW fractions before and after menadione displacement were compared with vehicle using direct analysis in real-time mass spectrometry (DART-MS).…”

“…The majority of urinary proteins in the HMW fraction were determined to be α2u-globulins through mass spectrometric analysis (LOC259246 and LOC298109). Proteins homologous to rat α2u-globulins are also involved in chemical communication in mice (Hurst, 2009;Papes et al, 2010;Vasudevan and Vyas, 2013), including sexual signaling (Roberts et al, 2010).…”