Olfactory Receptors, Vomeronasal Receptors, and the Organization of Olfactory Information

observed with a variety of molecular markers. For examThe main olfactory system of mammals recognizes the ple, the Ga protein Gi2 is expressed at high levels only universe of odorants using as many as a thousand rein apical neurons, while the Ga protein Go is expressed lated G protein–coupled receptors (Buck and Axel, at high levels only in basal neurons (Halpern et al., 1995; 1991). Oddly enough, the sensory potential of this vast Berghard and Buck, 1996). The expression of V1Rs was family is not exploited by the mammalian vomeronasal only observed in the apical cell layer, suggesting that a organ, a separate olfactory organ in the nasal septum, second class of receptors might be found in the basal which expresses a completely independent family of vomeronasal neurons. For two groups, the starting stratreceptor proteins (Dulac and Axel, 1995). Two papers egy for identifying these receptors was a search for genes in this issue of Cell (Herrada and Dulac, 1997; Matsunami expressed in Go-expressing vomeronasal neurons. and Buck, 1997) and a paper in a current issue of Neuron The Buck and Dulac groups used the same single(Ryba and Tirindelli, 1997) describe the cloning of yet a cell PCR approach that was used to identify the V1Rs third distinct class of mammalian olfactory receptors but began with cells that expressed Go and not Gi2. cDNA expressed by a subset of vomeronasal sensory neurons. libraries from single vomeronasal neurons that exDespite the patchwork of different candidate receptor pressed the Go mRNA were probed with cDNA from the systems used in olfaction, analysis of receptor expressame cell or from a different individual vomeronasal cell. sion in the different sensory systems reveals common Receptor clones were identified because they hybridfeatures that may organize olfactory pathways. ized strongly to cDNA from the starting cell, but did not Olfactory cues from predators, prey, or members of an hybridize to cDNA from the other cell. The Ryba group animal’s own species can elicit striking species-specific isolated the receptors by good luck: they probed a VNO behavioral and hormonal responses. In mammals, many cDNA library with mixed probe of olfactory receptors innate social and sexual responses are mediated through and found what turned out to be a V2R clone, despite the vomeronasal organ (VNO; Halpern, 1987). For examthe fact that V2Rs have no sequence homology to ORs. ple, male rodents require an intact vomeronasal organ The new receptors identified by all three groups correto mate efficiently with females and to respond aggresspond to a family of about 100 genes that are related sively to intruder males. In female rodents, activation of to the metabotropic glutamate receptors and the extrathe vomeronasal organ can trigger estrus in the prescellular calcium-sensing receptor, and more distantly ence of a male or the termination of pregnancy in the related to the GABA-B receptor. Other receptors in this presence of an unfamiliar male. Although the vomerofamily have a large extracellular domain that is implinasal organ can also recognize other cues—snake vocated in ligand binding followed by seven predicted meronasal neurons respond to prey—and the main membrane spanning domains.The V2Rs share this overolfactory system can also recognize pheromones, VNO all structure, unlike the smaller V1Rs and ORs that confunction appears to be strongly linked to instinctive sist mostly of seven membrane-spanning regions. Thus, behaviors. the ORs, the V1Rs, and the new V2Rs are completely Vomeronasal sensory neurons are distinct from olfacunrelated to one another and are derived from different tory neurons in their morphology (vomeronasal neurons branches of the G protein–coupled receptor superfamhave microvilli, olfactory neurons have cilia) and in the ily. Moreover, the olfactory and chemosensory recepsignal transduction components that they express. Oltors identified in C. elegans represent several additional factory neurons express the Gs-like protein Golf and G protein–coupled receptor classes that are essentially seven transmembrane domain receptors distantly reunrelated to each other and unrelated to any of the lated to adrenergic receptors and serotonin receptors vertebrate receptors (Troemel et al., 1995; Sengupta et (Buck and Axel, 1991). Vomeronasal neurons do not al., 1996). Transmembrane guanylyl cyclases might also express the classical olfactory receptors, nor do they function in chemoreception (Yu et al., 1997). These express Golf. Instead, VNO neurons express candidate results reveal the tremendous opportunism of the olfacreceptors that were previously identified using a singletory system: during evolution, it has diversified an ascell PCR strategy to find genes expressed at high levels sortment of receptors that appear to share nothing more in a subset of vomeronasal neurons (Dulac and Axel, than the ability to utilize G protein signaling pathways. 1995; the three groups use three nomenclatures for The olfactory receptors in insects have been refractory these receptors, which will be called V1Rs here). The to identification using homology-based approaches, so V1R genes comprise a family of 30–100 genes that eninsects may have found yet another molecular solution code proteins with seven predictedmembrane spanning to the problem of recognizing odorants.