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TRPA1 – Thermosensory and Chemosensory properties and Evolution

21Oct11

Paul Garrity, Professor at Brandeis University lectured about TRPA

Paul Garrity, PhD

Just saw Paul Garrity present an interesting story on the function and evolution of TRPA1–a chemical and temperature sensitive cation channel of the transient receptor potential family. He initially discovered TRPA1’s role in thermosensation using an RNAi screening of drosophila larvae on a thermal gradient.

As small ectotherms (a term which essentially means cold-blooded), drosophila must behaviorally regulate their temperature. If you put larvae on an uncomfortably hot part of a thermal gradient they will wander towards a cooler area. However with translation of TRPA1 is disrupted with RNA interference, larvae travel in all directions without regard to the heat.

They found TRPA1 was expressed in the front of the brain and probiscus, and using explants from the brain showed that the cells were directly responsive to temperature (and cells from TRPA1 KOs were not).

The group then compared their previous work on Drosophila melanogaster’s TRPA1, to that of a desert species–Drosophila mojavensis. They found that mojavensis’s TRPA1 channel had an elevated threshold for activation, and that larvae behavior preferred correspondingly higher temperatures on a heat plate. (Garrity is also interested in using TRPA1 as a transgene to activate certain groups of neurons. He calls this “thermogenetics” and says it could be used complementarily to optognetics. While there are still kinks to work out before it can be used in mammals, in Drosophila to channels have 1,000x higher conductance that optogenetic proteins.)

Drosophila Mojavensis up close

Drosophila Mojavensis

TRPA1 also responds to a variety of chemical signals include cinnamaldehyde, alicin (which gives onions their tear-evoking properties), tear gas, acrolein (which gives the acrid smell of burnt fat), AITC (found in Wasabi). Although structurally quite different, these molecules are all reactive electrophiles. It is very adaptive for animals to be able to detect and avoid this molecules because they react with protein, DNA, RNA, and lipids and are toxic and mutagenic in high concentrations. Most are produced by plants that store them in inactive forms that then are activated during the chewing and eating process. Some like acrolein are produced by our own body as a way of detecting damage. (TRPA can additionally detect intracellular pH drops and heavy metal poisoning.)

TRPA1 structure and activators

TRPA1 structure and activators

The multisensory responses of TRP channels bring up the question, how can drosophila tell the difference between toxic chemicals and a temperature response. It seems that there are actually two transcripts of the protein which code different isoforms–A which is expressed in the proboscis and acts as a chemosensor, and B which is expressed in the front of the brain and responds to both temperature and chemicals.

My friend and his mother both feel nothing when cutting onions. Is this common? I wonder if I should recruit them as subjects for a genetic study…

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