The molecular architecture of odor and pheromone sensing in mammals

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Abstract

exposure of a female to a male that is genetically differ-ent from the inseminating male (the Bruce Effect). In the Boston, Massachusetts 02115 Bruce Effect, it appears that a pheromone effect can be coupled with the detection of " individuality cues " that result from genetic variation within a species, including Olfaction is an ancient sense. Its precursors can be differences at major histocompatibility loci. found in the most primitive single-celled organisms, re-flecting the need of every organism to sense its chemical milieu. In mammals, the olfactory system can detect and Odor and Pheromone Circuits distinguish a vast number of volatile chemicals with a In mammals, odorants are detected in the olfactory epi-large variety of structures (Beets, 1970; Shepherd, 1988). thelium (OE) that lines the nasal cavity (Shepherd, 1988) It seems to have evolved to sense almost any volatile (Figure 1). Signals generated in olfactory sensory neu-chemical it might encounter. However, the olfactory sys-rons in the OE in response to odorants are relayed tem is also responsible for the sensing of pheromones, through the main olfactory bulb (MOB) to the olfactory chemicals released by animals that act on conspecifics cortex (OC) and then to other brain areas. Via these to regulate populations of animals and their social inter-pathways, odor signals ultimately reach higher cortical actions (Wilson, 1963; Shepherd, 1988). Pheromones areas involved in the conscious perception of odors, as elicit programmed neuroendocrine changes and innate well as limbic areas, such as the amygdala and hypothal-behaviors, suggesting a need for a very precise recogni-amus, that are involved in emotional and motivational tion process. responses. How does the olfactory system meet these dual re-Most mammals have a second olfactory sense organ, quirements for general odor sensing and the generation called the vomeronasal organ (VNO) (Figure 1). The VNO of stereotyped responses to specific pheromones? is a tubular structure in the nasal septum that is con-Studies in both insects and mammals suggest that it nected to the nasal cavity by a small duct. Removal of does it by segregating odor and pheromone detection the VNO, or severing its connection to the brain, inter-in different sensory neurons and in different neural path-feres with pheromone effects but not with general odor ways in the brain (Halpern, 1987; Wysocki and Meredith, sensing. Although some pheromones are sensed in the 1987; Hildebrand and Shepherd, 1997). Structural and OE (Dorries et al., 1997), these observations have sug-functional studies of these pathways have provided in-gested that the VNO may be specialized to detect phero-sight into many aspects of odor and pheromone sensing mones (Halpern, 1987; Wysocki and Meredith, 1987; (Halpern, 1987; Kauer, 1987; Wysocki and Meredith, Keverne, 1999). Sensory neurons in the VNO are con-1987; Shepherd, 1988; Buck, 1996; Hildebrand and nected to the accessory olfactory bulb (AOB). From Shepherd, 1997; Mori et al., 1999). In recent years, the there, signals are transmitted to areas of the amygdala discovery of multigene families encoding olfactory re-and hypothalamus that have been implicated in certain ceptors has provided molecular tools with which to fur-pheromone effects and are, for the most part, different ther explore these processes in both vertebrates and from those that receive odor signals. invertebrates (Buck and Axel, 1991; Ngai et al., 1993; Troemel et al., 1995; Sengupta et al., 1996; Clyne et al., Receptors for Odorants and Pheromones 1999; Vosshall et al., 1999). This review will focus on The initial detection of olfactory stimuli is mediated by what these molecular studies have revealed about the three distinct families of olfactory receptors, each en-mechanisms underlying odor and pheromone sensing coded by a multigene family (Figure 2). One family of in mammals. ‫0001ف‬ genes codes for odorant receptors (ORs) in the OE (Buck and Axel, 1991). Comprising approximately 1% of the genomic complement of genes, this family is Odorants and Pheromones by far the largest identified in the genome of any species. Mammals can distinguish an enormous diversity of ORs are members of the 7 transmembrane domain, G odorants that vary in size, shape, functional groups, and protein-coupled receptor (GPCR) superfamily. They are charge (Beets, 1970). In contrast, only a few mammalian extremely diverse in amino acid sequence, consistent pheromones have been identified, though many differ-with an ability to recognize a wide variety of structurally ent pheromone effects that can be elicited by urine or diverse odorants (Buck and Axel, 1991; Levy et al., 1991; other bodily secretions have been described (Halpern, Lancet and Ben-Arie, 1993; Ngai et al., 1993; Mom-1987; Wysocki and Meredith, 1987; Novotny et al., 1990; baerts, 1999). Keverne, 1999). In rodents, these include stereotyped The other two olfactory receptor families are ex-male and female mating behaviors, aggressive behav-pressed in the VNO: the V1R family, with about 35 mem-iors by males or lactating females toward intruder males, bers (Dulac and Axel, 1995), and the V2R family, with about 150 members (Herrada and Dulac, 1997; Mat-sunami and Buck, 1997; Ryba and Tirindelli, 1997). So * E-mail: lbuck@hms.harvard.edu. Cell 612 formed in the membrane by a combination of the trans-membrane domains (Strader et al., 1995). Consistent with a similar mode of ligand binding in ORs, a single amino acid change in one transmembrane domain of an OR has been shown to alter its odorant specificity (Krautwurst et al., 1998). Curiously, many V2R cDNAs lack segments that en-code bits of the N terminal domain, resulting in truncated proteins that have no transmembrane domains. The missing segments appear to correspond to individual exons (Matsunami and Buck, 1997). However, it is not known whether variant mRNAs are generated from po-tentially functional genes by alternative RNA splicing or from pseudogenes in which one or more exons is aber-rant or absent. Why do the VNO and OE use different sensory recep-tors? One possibility is that the different receptor fami-lies are uniquely suited to the distinct functions they presumably subserve: the perceptual discrimination of a multitude of volatile chemicals versus the generation of programmed endocrine and behavioral responses to pheromones. Recent studies indicate that individual ORs can recognize multiple odorants (see below). V1Rs and V2Rs might, instead, be selective for specific phero-mones, thereby preventing inadvertent behavioral or physiological responses to inappropriate stimuli, such as odorants, or pheromones of a different species. Figure 1. The Neural Circuitry of Odor and Pheromone Sensing: the

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Buck, L. B. (2000, March 17). The molecular architecture of odor and pheromone sensing in mammals. Cell. Cell Press. https://doi.org/10.1016/S0092-8674(00)80698-4

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