The songwriter Noel Coward once declared that only mad dogs and Englishmen went out in the midday sun. Now MIT biologists have a third candidate--fruit flies with defects in a gene called dTrpA1.
National stereotypes aside, most living creatures know when they are too hot or too cold and need to move. In biology, it's called thermotactic behavior. But until this new work, no one had a good molecular explanation of how environmental temperature is sensed and how it governs behavior.
If this new role for Drosophila dTrpA1 holds up, it will be the first time a temperature-sensing protein has been implicated in mediating thermotaxis in animals.
The research, led by Paul Garrity, assistant professor of biology at MIT, will be presented December 8 at a meeting of the American Society for Cell Biology. Garrity's colleagues are biology graduate students Mark Rosenzweig (first author of the paper) and Timothy Tayler, MIT affiliate Karen Brennan, and Ardem Patapoutian of the Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation.
Knowing what's hot and what's not is vital for living things, as temperature affects behavior, development and physiology. And, of course, temperature above or below a certain range is harmful to many organisms.
To identify the bioactive molecules that control thermotaxis, the researchers chose the celebrated fruit fly, Drosophila melanogaster, for their experimental system, noting that both Drosophila adults and larvae are known to avoid extreme temperatures. With a new generation hatching every ten days, the fruit fly is also highly amenable to genetic analysis.
To identify regulators of thermotactic behavior, Garrity and colleagues focused on Drosophila genes that are members of the Transient Receptor Potential (TRP) family of ion channels. Ion channels are protein tunnels that shift the balance of intracellular and extracellular ion concentrations, regulating the ability of neurons to propagate messages. Several members of the TRP gene family have been shown to act as temperature-responsive ion channels in cultured cells.
Reasoning that temperature-responsive TRP channels could act as sensors to activate neurons in response to changes in temperature, the researchers surveyed the functions of seven Drosophila genes related to temperature-responsive TRPs in mammals to determine if the Drosophila genes might be involved in thermotaxis.
When placed on a temperature gradient generated by heating one half of an agar-covered plastic dish, Drosophila larvae quickly migrated away from the heated region into the cooler zone. Within minutes, few of the larvae were even near the heated zone. However, larvae in which expression of the dTrpA1 protein was greatly reduced by the use of an experimental genetic trick called RNA interference (RNAi) didn't seem to notice the heat. Instead, the dTrpA1-deficient larvae ended up randomly distributed between the heated and unheated zones.
This suggests that they either did not sense the difference in temperature along the gradient or that they were unable to properly translate the sensation of temperature into a behavioral response. Interestingly, previous studies have demonstrated that dTrpA1 is activated by warming when expressed in frog oocytes. The MIT researchers suggest that Drosophila may use dTrpA1 to sense environmental temperature, with the activation of dTrpA1 triggering neuronal signaling events that prompt larvae to avoid the heat.
Whatever the connection, say Rosenzweig and Garrity, "Our work demonstrates an essential role for dTrpA1 in thermosensory behavior and begins the characterization of a previously unknown thermosensory circuit in Drosophila." Meantime, the rest of us will thermotax toward the shade.
This work was funded by the Raymond and Beverly Sackler Foundation, a Whitehead Career Development Professorship, the NSF, and the NIH.