title: Ultrasensitive detection of amines by a trace amine-associated receptor.
abstract: The mammalian main olfactory pathway detects volatile chemicals using two families of G-protein-coupled receptors: a large repertoire of canonical odorant receptors and a much smaller set of trace amine-associated receptors (TAARs). The TAARs are evolutionarily conserved in vertebrates, including humans, suggesting an indispensible role in olfaction. However, little is known about the functional properties of TAARs when expressed in native olfactory sensory neurons. Here we describe experiments using gene targeting, electrophysiology, and optical imaging to study the response properties of TAAR-expressing sensory neurons and their associated glomeruli in mice. We show that olfactory sensory neurons that express a subset of the TAAR repertoire are preferentially responsive to amines. In addition, neurons expressing specific TAARs, TAAR3 or TAAR4, are highly sensitive and are also broadly tuned-responding to structurally diverse amines. Surprisingly, we find that TAAR4 is exquisitely sensitive, with apparent affinities for a preferred ligand, phenylethylamine, rivaling those seen with mammalian pheromone receptors. We provide evidence that this unprecedented sensitivity is mediated via receptor coupling to the canonical odorant transduction cascade. The data suggest that the TAARs are evolutionarily retained in the olfactory receptor repertoire to mediate high-sensitivity detection of a biologically relevant class of odorous stimuli.
authors: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors: Jingji
authors: J
authors: Zhang
authors: Rodrigo
authors: R
authors: Pacifico
authors: Dillon
authors: D
authors: Cawley
authors: Paul
authors: P
authors: Feinstein
authors: Thomas
authors: T
authors: Bozza
mesh_terms: D000588:Amines / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology / Q000379:methods; D018390:Gene Targeting; D006801:Humans; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D059906:Neuroimaging; D009812:Odorants; D009830:Olfactory Bulb / Q000502:physiology; D009831:Olfactory Mucosa / Q000502:physiology; D009833:Olfactory Pathways / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010675:Pheromones / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000095383:Trace Amine-Associated Receptors
chemical_list: D000588:Amines; D010675:Pheromones; D043562:Receptors, G-Protein-Coupled; C579632:TAAR3 protein, mouse; D000095383:Trace Amine-Associated Receptors; C579631:TAAR4 protein, mouse