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Division of Cell Signaling



Molecular Mechanisms of thermosensation and nociception

We mainly investigate molecular mechanisms of thermosensation and nociception by focusing on so called ‘thermosensitive TRP channels’. Among the huge TRP ion channel superfamily proteins, there are eleven thermosensitive TRP channels in mammals (TRPV1, TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8, TRPA1, TRPC5) whose temperature thresholds for activation range from cold to hot.  Because temperatures below 15oC and over 43oC are known to cause pain sensation in our body, some of the thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nociceptive receptors.  Some of the thermosensitive TRP channels are expressed in the organs or cells which are normally not exposed to the dynamic temperature changes.  We found that they contribute to the various cell functions under the body temperature conditions in the normal to febrile range. Molecular and cell biological, biochemical, developmental and electrophysiological (patch-clamp and calcium-imaging methods) techniques are utilized to clarify the molecular mechanisms of thermosensation and nociception.  In order to understand functions of thermosensitive TRP channels in vivo, we are also doing behavioral analyses using mice lacking the thermosensitive TRP channels. In the evolutionary process, organisms are thought to have adapted the changes in ambient temperature by altering the expression and functions of the thermosensitive TRP channels. Accordingly, we are characterizing the thermosensitive TRP channels from various species, which would help us to understand the mechanisms of thermosensation.  
 We are also investigating thermosensation in Drosophila (fruit flies) through behavioral analyses utilizing plenty of genetical tools. In addition, since TRP channels are nociceptors, we are developing novel insecticides/repellents that could be used to control insect pests.


Eleven thermosensitive TRP channels

Selected publications

①Structural basis for promiscuous action of monoterpenes on TRP channels. Comms, Biol. 4 (1): 293, 2021.
②Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement. Proc. Natl. Acad. Sci. USA 118 (17): e2012894118, 2021.
③Inhibition of TRPV1 and TRPA1 by mosquito and mouse saliva. Pain 163 (2): 299-307, 2022.
④Nociceptor-derived Reg3g prevents endotoxic death by targeting kynurenine pathway in microglia. Cell Rep. 38: 110462, 2022.
⑤Temperature and sweet taste integration in Drosophila. Curr. Biol.. 30 (11), 2051-2067, 2020.