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The Journal of Neuroscience, August 15, 2001, 21(16):6018-6025
Molecular Bases of Odor Discrimination: Reconstitution of
Olfactory Receptors that Recognize Overlapping Sets of Odorants
Kentaro
Kajiya1,
Koichiro
Inaki2,
Motonari
Tanaka1,
Tatsuya
Haga2,
Hiroshi
Kataoka1, and
Kazushige
Touhara1
1 Department of Integrated Biosciences, Graduate School
of Frontier Sciences and 2 Department of Neurochemistry,
Faculty of Medicine, The University of Tokyo, Tokyo 113, Japan
The vertebrate olfactory system discriminates a wide variety of
odorants by relaying coded information from olfactory sensory neurons
in the olfactory epithelium to olfactory cortical areas of the brain.
Recent studies have shown that the first step in odor discrimination is
mediated by ~1000 distinct olfactory receptors, which comprise the
largest family of G-protein-coupled receptors. In the present
study, we used Ca2+ imaging and single-cell reverse
transcription-PCR techniques to identify mouse olfactory neurons
responding to an odorant and subsequently to clone a receptor gene from
the responsive cell. The functionally cloned receptors were expressed
in heterologous systems, demonstrating that structurally related
olfactory receptors recognized overlapping sets of odorants with
distinct affinities and specificities. Our results provide direct
evidence for the existence of a receptor code in which the identities
of different odorants are specified by distinct combinations of odorant
receptors that possess unique molecular receptive ranges. We further
demonstrate that the receptor code for an odorant changes with odorant
concentration. Finally, we show that odorant receptors in human
embryonic kidney 293 cells couple to stimulatory G-proteins such
as G olf, resulting in odorant-dependent increases in cAMP. Odor
discrimination is thus determined by differences in the receptive
ranges of the odorant receptors that together encode specific odorant molecules.
Key words:
olfactory; odorant; receptor; single-cell RT-PCR; calcium
imaging; G-protein; cAMP; HEK293
Copyright © 2001 Society for Neuroscience 0270-6474/01/21166018-08$05.00/0
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