Transcript A metabotropic glutamate receptor variant functions as a taste receptor

A metabotropic glutamate
receptor variant functions as a
taste receptor
Nirupa Chaudhari
Ana Marie Landin
Stephen D. Roper
Sensation and Perception
Melanie Zeck, Presenter
November 29, 2004
The Tongue:
What you were taught…
The New Tongue
Question
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General: Is there really a fifth taste receptor?
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Specific: What is it and what is it sensitive for?
Alternatives
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No, there are only four
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Sweet
Sour
Salty
Bitter
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Yes, there are five
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UMAMI
Something else
Logic
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If evidence is discovered that a receptor in the
tongue has the same response properties as
would be expected from response curves to that
stimulus psychophysically, this suggests that this
receptor is a receptor for that stimulus.
If such a receptor for Umami-responses can be
found, then it can be concluded that a fifth
receptor exists and that it senses Umami.
Methods
Subjects: Harlan Sprague-Dawley rats
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a) Clone the glutamate receptor in the tongue of the rats
b) Use PCR to identify the relationship between the
receptor in the tongue and in the brain.
c) Compare functional properties of tongue receptor with
brain receptor (Response to Umami/Glutamate)
d) Compare functional properties of tongue receptor with
brain receptor to another substance that tastes like Umami
Results
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The cloned mGluR4 receptor in the tongue is
similar to the mGluR4 receptor in the brain.
It is only expressed in taste buds.
It is structurally similar but truncated.
In particular, the Glutamate binding region is very
short in the tongue-version (“taste-mGluR4”).
Results
Structure
PCR
Assay
Model
Results
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Taste-mGluR4 is much less sensitive to Glutamate than brainmGluR4, as would be expected by the concentrations encountered by
a taste receptor.
Brain-mGluR4 is sensitive to the Neurotransmitter Glutamate in
minute, microMolar concentrations. (2 μM brain vs. 280 μM taste)
Results
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Taste-mGluR4 reacts the same way (reduction in cAMP expression)
to L-AP4 (that tastes like Glutamate) as it does to L-MSG.
Again, brain-mGluR4 is much too sensitive to L-AP4 to be an
effective taste-receptor.
Results - Summary
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A truncated version of mGluR4 in the brain that is sensitive to the
Neurotransmitter Glutamate could be cloned in the tongue.
It is only expressed in taste buds.
Like the brain receptor, it is sensitive to L-MSG, but only if the
concentration of L-MSG is much higher, as is adequate for signaling
the presence of a substance on the tongue, as opposed to signaling
the presence of a neurotransmitter.
As would be expected if it is a Glutamate receptor, the response to
L-AP4 (which tastes like Glutamate) is similar to the response to
MSG directly.
Interpretation
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The four-receptor model of the tongue no
longer applies.
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There is at least one other basic taste receptor in
the tongue, which is sensitive for MSG.
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This receptor seems to be taste-mGluR4.
Problems
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All these results are only CONSISTENT with
the notion that taste-mGluR4 is a taste receptor
for Umami, but they do not prove the receptor’s
existence.
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How to prove that the receptor exists?
The Proof:
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a) Recording from taste-mGluR4 receptor in the
tongue, predicting behavioral response of an
animal trained to select Umami-tagged stimulus.
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b) Create a knock-out rat that has no such
receptor and show that it is unable to taste
Umami.
Comments
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Brain-receptors are sensitive to monosodium
glutamate in very small amounts.
Tongue receptors are sensitive to only large
amounts of glutamate.
It looks like the organism retained a mutated
version of an already developed receptor for
another function (!)
Comments, continued
This discovery also indicates—
many more discoveries are possible in the
areas of sensation and perception other than
vision science.