TY - JOUR
T1 - Ultrasensitive detection of amines by a trace amine-associated receptor
AU - Zhang, Jingji
AU - Pacifico, Rodrigo
AU - Cawley, Dillon
AU - Feinstein, Paul
AU - Bozza, Thomas
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/2/13
Y1 - 2013/2/13
N2 - 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, electro-physiology, 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.
AB - 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, electro-physiology, 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.
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U2 - 10.1523/JNEUROSCI.4299-12.2013
DO - 10.1523/JNEUROSCI.4299-12.2013
M3 - Article
C2 - 23407976
AN - SCOPUS:84873617088
VL - 33
SP - 3228
EP - 3239
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7
ER -