A second class of chemosensory receptors in the olfactory epithelium
Abstract
The mammalian olfactory system detects chemicals sensed as odours as well as social cues that stimulate innate responses. Odorants are detected in the nasal olfactory epithelium by the odorant receptor family, whose approximately 1,000 members allow the discrimination of a myriad of odorants. Here we report the discovery of a second family of receptors in the mouse olfactory epithelium. Genes encoding these receptors, called 'trace amine-associated receptors' (TAARs), are present in human, mouse and fish. Like odorant receptors, individual mouse TAARs are expressed in unique subsets of neurons dispersed in the epithelium. Notably, at least three mouse TAARs recognize volatile amines found in urine: one detects a compound linked to stress, whereas the other two detect compounds enriched in male versus female urine-one of which is reportedly a pheromone. The evolutionary conservation of the TAAR family suggests a chemosensory function distinct from odorant receptors. Ligands identified for TAARs thus far suggest a function associated with the detection of social cues.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TMA has been reported to influence signal transduction by direct interaction with a family of G protein-coupled receptors.
“whereas TMA has been reported to influence signal transduction by direct interaction with a family of G protein-coupled receptors (47).”
The highest subgroup cutoff of 0.2ppm converts to 2.6μM, and these low levels of TMAO have never been implicated in disease.
“In fact, the highest subgroup cutoff of 0.2ppm converts to 2.6µM. These low levels of TMAO have never been implicated in disease.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [171]
Male mice display 100-fold decreased liver Fmo3 mRNA compared to females, resulting in far lower natural levels of plasma TMAO.
“male mice display 100-fold decreased liver Fmo3 mRNA compared to females, resulting in far lower natural levels of plasma TMAO171.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [171]
Following ingestion of a TMA containing nutrient, distinct microbial enzyme systems participate in the generation of TMA, the precursor of TMAO.
“Following ingestion of a TMA containing nutrient (the choline moiety being the most abundant in a typical diet), distinct microbial enzyme systems participate in the generation of TMA, the precursor of TMAO158,171 (FIG. 5).”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [171]
Cites
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,148 · see citing works
A novel multigene family may encode odorant receptors: A molecular basis for odor recognition
Buck, L., & Axel, R. (1991) · Cell · doi:10.1016/0092-8674(91)90418-x · Cited by 4,987 · see citing works
Self-citationThe Synaptic Organization of the Brain
(2004) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195159561.001.1 · Cited by 3,550 · see citing works
Combinatorial Receptor Codes for Odors
Malnic, B., Hirono, J., Sato, T., & Buck, L. B. (1999) · Cell · doi:10.1016/s0092-8674(00)80581-4 · Cited by 2,302 · see citing works
Self-citationZagrean, L. (2014) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2014.529 · Cited by 1,926 · see citing works
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635 · see citing works
Continuous Fluorescence Monitoring of Rapid Cycle DNA Amplification
Wittwer, C. T., Herrmann, M. G., Moss, A. A., & Rasmussen, R. P. (2013) · BioTechniques · doi:10.2144/000114043 · Cited by 1,274 · see citing works
Continuous Fluorescence Monitoring of Rapid Cycle DNA Amplification
Wittwer, C. T., Herrmann, M. G., Moss, A. A., & Rasmussen, R. P. (1997) · BioTechniques · doi:10.2144/97221bi01 · Cited by 1,144 · see citing works
A zonal organization of odorant receptor gene expression in the olfactory epithelium
Ressler, K. J., Sullivan, S. L., & Buck, L. B. (1993) · Cell · doi:10.1016/0092-8674(93)90145-g · Cited by 1,054 · see citing works
Self-citationTrace amines: Identification of a family of mammalian G protein-coupled receptors
Borowsky, B., Adham, N., JONES, K. A., Raddatz, R., Artymyshyn, R. P., Ogozalek, K. L., Durkin, M. M., Lakhlani, P. P., Bonini, J. A., Pathirana, S. M., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151105198 · Cited by 912 · see citing works
The olfactory receptor gene superfamily of the mouse
Zhang, X., & Firestein, S. (2002) · Nature Neuroscience · doi:10.1038/nn800 · Cited by 897 · see citing works
G olf : an Olfactory Neuron Specific-G Protein Involved in Odorant Signal Transduction
Jones, D. T., & Reed, R. R. (1989) · Science · doi:10.1126/science.2499043 · Cited by 888 · see citing works
Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium
Vassar, R. J., Ngai, J., & Axel, R. (1993) · Cell · doi:10.1016/0092-8674(93)90422-m · Cited by 874 · see citing works
The G protein-coupled receptor repertoires of human and mouse
Vassilatis, D. K., Hohmann, J. G., Zeng, H., Li, F., Ranchalis, J., Mortrud, M. T., Brown, A., Rodriguez, S. S., Weller, J. R., Wright, A. C., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0230374100 · Cited by 779 · see citing works
Structure and function of the vomeronasal system: an update
Halpern, M. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00103-5 · Cited by 639 · see citing works
Identification of Ligands for Olfactory Receptors by Functional Expression of a Receptor Library
Krautwurst, D., Yau, K., & Reed, R. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81716-x · Cited by 598 · see citing works
Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse
Serizawa, S., Miyamichi, K., Nakatani, H., Suzuki, M., Saito, M., Yoshihara, Y., & Sakano, H. (2003) · Science · doi:10.1126/science.1089122 · Cited by 540 · see citing works
The Molecular Architecture of Odor and Pheromone Sensing in Mammals
Buck, L. B. (2000) · Cell · doi:10.1016/s0092-8674(00)80698-4 · Cited by 475 · see citing works
Self-citationA candidate taste receptor gene near a sweet taste locus
Montmayeur, J., Liberles, S. D., Matsunami, H., & Buck, L. B. (2001) · Nature Neuroscience · doi:10.1038/87440 · Cited by 472 · see citing works
Self-citationOlfactory Inputs to Hypothalamic Neurons Controlling Reproduction and Fertility
Yoon, H., Enquist, L. W., & Dulac, C. G. (2005) · Cell · doi:10.1016/j.cell.2005.08.039 · Cited by 435 · see citing works
Kajiya, K., Inaki, K., Tanaka, M., Haga, T., Kataoka, H., & Touhara, K. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-16-06018.2001 · Cited by 366 · see citing works
The mouse olfactory receptor gene family
Godfrey, P. A., Malnic, B., & Buck, L. B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308051100 · Cited by 360 · see citing works
Self-citationDeficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes
Punta, K. D., Leinders‐Zufall, T., Rodríguez, I., Jukam, D., Wysocki, C. J., Ogawa, S., Zufall, F., & Mombaerts, P. (2002) · Nature · doi:10.1038/nature00955 · Cited by 357 · see citing works
Feedback Loops Link Odor and Pheromone Signaling with Reproduction
Boehm, U., Zou, Z., & Buck, L. B. (2005) · Cell · doi:10.1016/j.cell.2005.09.027 · Cited by 331 · see citing works
Self-citationSpehr, M., Kelliher, K. R., Li, X., Boehm, T. L. J., Leinders‐Zufall, T., & Zufall, F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4939-05.2006 · Cited by 301 · see citing works
A renaissance in trace amines inspired by a novel GPCR family
Lindemann, L., & Hoener, M. C. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.03.007 · Cited by 290 · see citing works
Increased stress response and β–phenylethylamine in MAOB–deficient mice
Grimsby, J. S., Tóth, M., Chen, K., Kumazawa, T., Klaidman, L. K., Adams, J. D., Jr., Karoum, F., Gál, J., & Shih, J. C. (1997) · Nature Genetics · doi:10.1038/ng1097-206 · Cited by 258 · see citing works
The sense of smell: genomics of vertebrate odorant receptors
Young, J. M. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.10.1153 · Cited by 209 · see citing works
Pheromones, binding proteins and receptor responses in rodents
Novotný, M. V. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310117 · Cited by 203 · see citing works
Fiering, S., Roederer, M., Nolan, G. P., Micklem, D., Parks, D. R., & Herzenberg, L. A. (1991) · Cytometry · doi:10.1002/cyto.990120402 · Cited by 186 · see citing works
Restrepo, D., Arellano, J., Oliva, A. M., Schaefer, M. L., & Lin, W. (2004) · Hormones and Behavior · doi:10.1016/j.yhbeh.2004.02.009 · Cited by 173 · see citing works
A cGMP-signaling pathway in a subset of olfactory sensory neurons
Meyer, M. R., Angele, A., Kremmer, E., Kaupp, U. B., & Müller, F. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.19.10595 · Cited by 172 · see citing works
Durocher, Y., Perret, S., Thibaudeau, E., Gaumond, M.-H., Kamen, A., Stocco, R., & Abramovitz, M. (2000) · Analytical Biochemistry · doi:10.1006/abio.2000.4698 · Cited by 110 · see citing works
The repertoire of trace amine G-protein-coupled receptors: large expansion in zebrafish
Gloriam, D. E. I., Bjarnadóttir, T. K., Yan, Y., Postlethwait, J. H., Schiöth, H. B., & Fredriksson, R. (2005) · Molecular Phylogenetics and Evolution · doi:10.1016/j.ympev.2004.12.003 · Cited by 103 · see citing works
Excretion of β-Phenethylamine Is Elevated in Humans After Profound Stress
Paulos, M. A., & Tessel, R. E. (1982) · Science · doi:10.1126/science.7063846 · Cited by 72 · see citing works
Metabolic Phenotyping of Nude and Normal (Alpk:ApfCD, C57BL10J) Mice
McKee, C. L. G., Wilson, I. D., & Nicholson, J. K. (2006) · Journal of Proteome Research · doi:10.1021/pr050255h · Cited by 64 · see citing works
Receptors of mammalian trace amines
Lewin, A. H. (2006) · The AAPS Journal · doi:10.1208/aapsj080116 · Cited by 59 · see citing works
Identification of puberty‐accelerating pheromones in male mouse urine
Nishimura, K., Utsumi, K., Yuhara, M., et al. (1989) · Journal of Experimental Zoology · doi:10.1002/jez.1402510306 · Cited by 50 · see citing works
Validation of 1H NMR spectroscopy as an analytical tool for methylamine metabolites in urine
Lee, M. B. H., Storer, M., Blunt, J. W., et al. (2005) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.09.004 · Cited by 49 · see citing works
Discovery of a null mutation in a human trace amine receptor gene
Vanti, W. B., Muglia, P., Nguyen, T., Cheng, R., Kennedy, J. L., George, S. R., & O’Dowd, B. F. (2003) · Genomics · doi:10.1016/s0888-7543(03)00173-3 · Cited by 36 · see citing works
Analysis of puberty‐accelerating pheromones
Price, M. A., & Vandenbergh, J. G. (1992) · Journal of Experimental Zoology · doi:10.1002/jez.1402640107 · Cited by 27 · see citing works
Cold-restraint stress and urinary endogenous β-phenylethylamine excretion in rats
Snoddy, A. M., Heckathorn, D., & Tessel, R. E. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90054-1 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386 · see citing works
Dietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
Chen, M.-L., Yi, L., Zhang, Y., Zhou, X., Ran, L., Yang, J., Zhu, J.-D., Zhang, Q.-Y., & Mi, M.-T. (2016) · mBio · doi:10.1128/mbio.02210-15 · Cited by 754 · see citing works
“a specific receptor or whether it acts to alter signaling pathways indirectly by altering the protein conformation (that is, via allosteric effects), whereas TMA has been reported to influence signal transduction by direct interaction with a family of G proteincoupled receptors (47).”
BackgroundAn initial evaluation of the functions of human olfaction
Stevenson, R. J. (2010) · Chemical Senses · doi:10.1093/chemse/bjp083 · Cited by 689 · see citing works
Trace amine-associated receptors and their ligands
Zucchi, R., Chiellini, G., Scanlan, T. S., & Grandy, D. K. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706948 · Cited by 314 · see citing works
Opsins and clusters of sensory G-protein-coupled receptors in the sea urchin genome
Raible, F., Tessmar-Raible, K., Arboleda, E., Kaller, T., Bork, P., Arendt, D., & Arnone, M. I. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.070 · Cited by 170 · see citing works
A family of non-GPCR chemosensors defines an alternative logic for mammalian olfaction
Greer, P. L., Bear, D. M., Lassance, J.-M., Bloom, M. L., Tsukahara, T., Pashkovski, S. L., Masuda, F. K., Nowlan, A. C., Kirchner, R., Hoekstra, H. E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.001 · Cited by 148 · see citing works
Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2
Babusyte, A., Kotthoff, M., Fiedler, J., & Krautwurst, D. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0912433 · Cited by 146 · see citing works
Human Trace Amine-Associated Receptor TAAR5 Can Be Activated by Trimethylamine
Wallrabenstein, I., Kuklan, J., Weber, L., Zborala, S., Werner, M., Altmüller, J., Becker, C., Schmidt, A., Hatt, H., Hummel, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054950 · Cited by 122 · see citing works
Vasopressin, oxytocin, and social odor recognition
Wacker, D. W., & Ludwig, M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.08.014 · Cited by 112 · see citing works
Processing of body odor signals by the human brain
Pause, B. M. (2012) · Chemosensory Perception · doi:10.1007/s12078-011-9108-2 · Cited by 107 · see citing works
Deep Sequencing of the Murine Olfactory Receptor Neuron Transcriptome
Kanageswaran, N., Demond, M., Nagel, M., Schreiner, B. S. P., Baumgart, S., Scholz, P., Altmüller, J., Becker, C., Doerner, J. F., Conrad, H., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0113170 · Cited by 85 · see citing works
Largest Vertebrate Vomeronasal Type 1 Receptor Gene Repertoire in the Semiaquatic Platypus
Grus, W. E., Shi, P., & Zhang, J. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm157 · Cited by 83 · see citing works
Volatile signals during pregnancy: a possible chemical basis for mother–infant recognition
Vaglio, S., Minicozzi, P., Bonometti, E., Mello, G., & Chiarelli, B. (2009) · Journal of Chemical Ecology · doi:10.1007/s10886-008-9573-5 · Cited by 53 · see citing works
Aberrant methylation of gene associated CpG sites occurs in borderline personality disorder
Teschler, S., Bartkuhn, M., Künzel, N., Schmidt, C., Kiehl, S., Dammann, G., & Dammann, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084180 · Cited by 36 · see citing works
G protein-coupled receptor mediated trimethylamine sensing
Suska, A., Ibáñez, A. B., Lundström, I., & Berghard, A. (2009) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2009.08.012 · Cited by 26 · see citing works
- Authors
- Liberles, S. D., & Buck, L. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Buck, Linda B.
- Venue
- Nature
- Published
- 2006-07-30
- Volume
- 442
- Issue
- 7103
- Pages
- 645-650
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2070907334
- Cited by
- 791
- References
- 42
- Citations by year
- 2026: 18 · 2025: 39 · 2024: 32 · 2023: 25 · 2022: 30 · 2021: 44 · 2020: 45 · 2019: 45 · 2018: 39 · 2017: 31 · 2016: 48 · 2015: 46 · 2014: 39 · 2013: 39 · 2012: 34
- FWCI
- 22.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- trace amine-associated receptors, olfactory epithelium, chemosensory receptors, olfactory receptors, volatile amines, urine, pheromones, social cues, stress detection, sexual dimorphism, evolutionary conservation, olfactory sensory neurons, mating behavior
- MeSH terms
- Trace Amine-Associated Receptors, Amines, Animals, Cues, Female, Humans, Male, Mice, Inbred C57BL, Neurons, Odorants, Olfactory Mucosa, Organ Specificity, Pheromones, Sexual Maturation, Stress, Physiological, Substrate Specificity, Urine, Volatilization, Gene Expression Profiling, Receptors, G-Protein-Coupled, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
