A metabotropic glutamate receptor variant functions as a taste receptor

1
A metabotropic glutamate receptor variant
functions as a taste receptor

• Nirupa Chaudhari
• Ana Marie Landin
• Stephen D. Roper

2
Sensation and Perception

• Melanie Zeck, Presenter
• November 29, 2004

3
The TongueWhat you were taught
4
The New Tongue
5
Question

• General Is there really a fifth taste receptor?
• Specific What is it and what is it sensitive
  for?

6
Alternatives

• No, there are only four
• Sweet
• Sour
• Salty
• Bitter

• Yes, there are five
• UMAMI
• Something else

7
Logic

• 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.

8
Methods

• Subjects Harlan Sprague-Dawley rats
• 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

9
Results

• 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).

10
Results
Structure
Model
PCR
Assay
11
Results

• Taste-mGluR4 is much less sensitive to Glutamate
  than brain-mGluR4, 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)

12
Results

• 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.

13
Results - Summary

• 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.

14
Interpretation

• The four-receptor model of the tongue no longer
  applies.
• There is at least one other basic taste receptor
  in the tongue, which is sensitive for MSG.
• This receptor seems to be taste-mGluR4.

15
Problems

• All these results are only CONSISTENT with the
  notion that taste-mGluR4 is a taste receptor for
  Umami, but they do not prove the receptors
  existence.
• How to prove that the receptor exists?

16
The Proof

• a) Recording from taste-mGluR4 receptor in the
  tongue, predicting behavioral response of an
  animal trained to select Umami-tagged stimulus.
• b) Create a knock-out rat that has no such
  receptor and show that it is unable to taste
  Umami.

17
Comments

• 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 (!)

18
Comments, continued

• This discovery also indicates
• many more discoveries are possible in the
  areas of sensation and perception other
  than vision science.