Take a TRP to beat the heat.

Temperature is a ubiquitous physical variable with a profound impact on living organisms. Obviously, because of its detrimental effects on cellular biochemistry and integrity, extreme temperature must be detected and avoided. Even subtle differences in environmental temperature, however, can provide valuable information regarding the presence of food, companions, predators, or just a cozy place to rest. As a consequence, organisms from bacteria to mammals have evolved mechanisms to survey their thermal landscapes. Thermotaxis, migration towards a particular range of temperatures, has been studied in numerous vertebrate and invertebrate species, and a few molecular components of their thermotactic machinery have been identified. For example, in Escherichia coli, where thermotaxis is regulated by a twocomponent system that directs the activity of a flagellar motor, cell-surface amino acid receptors of the methylaccepting chemotaxis protein family have been shown to exhibit opposite patterns of intracellular signaling, depending on whether the ambient temperature is closer to 16°C or 27°C (Nishiyama et al. 1997). In Caenorhabditis elegans, genetic screens have led to the identification of two cyclic nucleotide gated channels, TAX-2 and TAX-4, whose elimination results in impaired thermotaxis (Coburn and Bargmann 1996; Komatsu et al. 1996) and a third related channel, cng-3, required for normal tolerance to elevated temperatures (Cho et al. 2004). However, the actual temperature-transducing molecules in worms have yet to be defined. Indeed, much remains to be learned regarding the mechanistic details of thermotaxis and the degree to which this process is evolutionarily conserved. In this issue, Rosenzweig et al. (2005) present compelling evidence that dTRPA1, an ion channel of the Transient Receptor Potential (TRP) family (Montell et al. 2002), is critical for thermotaxis behavior in Drosophila larvae. The rationale underlying this study is that one invertebrate TRP channel (dTRPA1) (Viswanath et al. 2003) and six vertebrate TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) have been demonstrated electrophysiologically to undergo channel opening in response to heat or cold, over a range of temperatures that is distinct for each channel (Caterina et al. 1997, 1999; Guler et al. 2002; McKemy et al. 2002; Peier et al. 2002a,b; Smith et al. 2002; Watanabe et al. 2002; Xu et al. 2002; Story et al. 2003). For instance, TRPV1, TRPM8, or dTRPA1 can be activated by temperatures 43° C, 23°C–28°C, or 27°C, respectively (Caterina et al. 1997; McKemy et al. 2002; Peier et al. 2002a; Viswanath et al. 2003). In addition, gene disruption experiments have shown that TRPV1 is essential for normal heat-evoked pain sensation and thermal hyperalgesia in mice (Caterina et al. 2000; Davis et al. 2000), while a Drosophila mutant lacking another TRP channel, Painless, shows impairment in avoidance responses to noxious heat or mechanical stimuli (Tracey et al. 2003). Guided by these findings, and by the prior demonstration that Drosophila larvae and adults exhibit thermotaxis (Sayeed and Benzer 1996; Zars 2001; Liu et al. 2003), Rosenzweig et al. (2005) use in vivo short interfering RNA (siRNA) to disrupt expression of candidate thermosensory TRP channels, either individually or in combination, in Drosophila embryos. In particular, they focused on the genes encoding the Drosophila TRPV, TRPM, and TRPAs, as members of these TRP subfamilies are known “thermoTRPs.” Simultaneous knockdown of a transgene encoding a neuronally expressed GFP provided an efficient positive control for this procedure. Then, using a simple behavioral assay, the authors evaluated thermotaxis in the resulting larvae. Rosenzweig et al. (2005) first demonstrate that when late firstand early second-instar larvae that have been raised at an optimum growth temperature of 24°C are released into the 31°C–35°C zone of a 27°C–41°C thermal gradient, they migrate within 25 min towards cooler temperatures, closer to their growth temperature (Fig. 1). However, when expression of Drosophila TRPA subtypes or that of dTRPA1 alone is disrupted at the embryonic stage using siRNA, they found that the resulting larvae no longer prefer the cooler temperatures, and distribute themselves evenly at temperatures above and below the release zone (Fig. 1). Critical to the interpretation of this behavioral phenotype is the elegant array of control experiments the authors include. For example, they demonstrate that dTRPA1 “knockdown” larvae exhibit normal motility in the thermal gradient, despite achieving a different distribution. They also observed no change in avoidance of an olfactory repellent (N-octyl acetate) or avoidance responses following contact with a 55°C probe, suggesting that the thermotaxis phenotype reflects a remarkably specific defect in responsiveness to Corresponding author. E-MAIL cmontell@jhmi.edu; FAX (410) 614-9573. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1294905.