TY - JOUR T1 - A Hot-Sensing Cold Receptor: C-Terminal Domain Determines Thermosensation in Transient Receptor Potential Channels JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4835 LP - 4840 DO - 10.1523/JNEUROSCI.5080-05.2006 VL - 26 IS - 18 AU - Sebastian Brauchi AU - Gerardo Orta AU - Marcelo Salazar AU - Eduardo Rosenmann AU - Ramon Latorre Y1 - 2006/05/03 UR - http://www.jneurosci.org/content/26/18/4835.abstract N2 - Temperature transduction in mammals is possible because of the presence of a set of temperature-dependent transient receptor potential (TRP) channels in dorsal root ganglia neurons and skin cells. Six thermo-TRP channels, all characterized by their unusually high temperature sensitivity (Q10 > 10), have been cloned: TRPV1–4 are heat activated, whereas TRPM8 and TRPA1 are activated by cold. Because of the lack of structural information, the molecular basis for regulation by temperature remains unknown. In this study, we assessed the role of the C-terminal domain of thermo-TRPs and its involvement in thermal activation by using chimeras between the heat receptor TRPV1 and the cold receptor TRPM8, in which the entire C-terminal domain was switched. Here, we demonstrate that the C-terminal domain is modular and confers the channel phenotype regarding temperature sensitivity, channel gating kinetics, and PIP2 (phosphatidylinositol-4,5-bisphophate) modulation. Thus, thermo-TRP channels contain an interchangeable specific region, different from the voltage sensor, which allows them to sense temperature stimuli. ER -