A second class of chemosensory receptors in the olfactory epithelium
 Nature, Vol. 442, No 7103, P. 645-650 | |
 Рис.1. | Taar genes are expressed in subsets of olfactory sensory neurons.  Рис.2. | Taar genes are selectively expressed in the olfactory epithelium.  Рис.3. | Each Taar gene defines a unique subset of olfactory sensory neurons.  Рис.4. | TAARs recognize volatile amines.  Рис.5. | mTAAR5 is activated by urine from sexually mature male mice. | Система обоняния млекопитающих определяет химические соединения, ощущаемые как запахи, а также как социальные сигналы, которые стимулируют внутренние реакции. Запахи определяются носовым обонятельным эпителием с помощью семейства рецепторов запаха, чьё количество около 1000 позволяет различать мириады пахучих веществ. Описывается открытие второго семейства рецепторов в обонятельном эпителии мышей. Гены, кодирующие эти рецепторы, названы 'trace amine-associated receptors' (TAARs), они присутствуют у людей, мышей и рыб. Подобно рецепторам запахов, индивидуальные TAARs мышей экспрессируются в виде уникальных субнаборов нейронов, разбросанных по эпителию. Отметим, что по крайней мере, три TAARs у мышей распознают летучие амины, обнаруживаемые в моче: один выявляет соединение, связанное со стрессом, тогда как два других выявляют соединения, обогащенные в моче самцов по сравнению с самками - одно из которых известно как феромон. Эволюционно законсервированное TAAR семейство подтверждает хемосенсорную функцию, отличную от от рецепторов запахов. Лиганды, идентифицированные для TAARs, указывают на функцию связанную с детекцией социальных сигналов.
The first step in odour perception is the detection of odorants by G protein-coupled odorant receptors on olfactory sensory neurons (OSNs) in the nasal olfactory epithelium1,2,3. In response to odorants, OSNs transmit signals to the brain, thereby generating odour perceptions2,4. Each OSN expresses a single functional odorant receptor gene5, and OSNs with the same odorant receptor are randomly dispersed within one olfactory epithelial zone6,7. Consistent with their ability to detect and discriminate diverse odorants, mammals have as many as 1,000 different odorant receptors that vary in protein sequence8,9,10 and are used combinatorially to detect different odorants and encode their unique identities5. These features of the odorant receptor family would seem to account easily for the odorant recognition abilities of mammals. However, a small percentage of OSNs lack Golf11, the G protein through which odorant receptors signal12, suggesting that they might express another class of chemosensory receptor. In addition, small peptides that bind major histocompatibility complex (MHC) proteins can stimulate some OSNs13, suggesting that those OSNs might express a class of receptor that detects peptides rather than small volatile odorants. Finally, although many pheromones are detected in the vomeronasal organ—an olfactory structure with receptors that differ from odorant receptors3,14—responses to some mouse pheromones involve the olfactory epithelium15,16,17, raising the possibility that the olfactory epithelium also contains a dedicated class of pheromone receptors.
A second family of receptors in the olfactory epithelium To explore whether there might be other types of chemosensory receptors in the olfactory epithelium, we initiated a search for additional G protein-coupled receptors (GPCRs) expressed by mouse OSNs. In preliminary studies, we found that tissue fixation with glutaraldehyde reveals endogenous -galactosidase activity present in OSNs, but not in other olfactory epithelial cells (Supplementary Fig. S1). To obtain an enriched population of OSNs, we treated dissociated olfactory epithelial cells with a fluorescent -galactosidase substrate—fluorescein di-(-galactopyranoside)18—and then isolated labelled cells by fluorescence-activated cell sorting. Using RNA from the sorted cells, we prepared complementary DNA, which we then used in real-time quantitative PCR (qPCR) reactions with primers matching GPCRs not previously implicated in odour, pheromone or taste detection19. cDNAs encoding individual GPCRs were quantified using standard curves obtained from qPCR reactions with titrations of mouse genomic DNA...
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