Nirupa Chaudhari Ana Marie Landin Stephen D. Roper 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 General: Is there really a fifth taste receptor? Specific: What is it and what is it sensitive for?

Alternatives No, there are only four Yes, there are five Sweet Sour Salty Bitter Yes, there are five UMAMI Something else

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.

Subjects: Harlan Sprague-Dawley rats 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

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”).

Results Structure Model PCR Assay

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)

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.

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.

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.

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 receptor’s existence. How to prove that the receptor exists?

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.

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 (!)

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