The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia
5 affiliations
- 1Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- 2Guangdong Institute of Intelligence Science and Technology, Zhuhai, China
- 3Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China
- 4State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
- 5Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
Abstract
In mammals, heat sensation is primarily mediated by thermosensitive channels, particularly transient receptor potential (TRP) channels, in dorsal root ganglion (DRG) neurons. However, whether additional channels contribute to noxious heat detection remains unclear. Here, we investigated the role of the mechanosensitive cation channel TMEM63B in DRG neurons and unexpectedly discovered its involvement in noxious thermosensation rather than mechanosensation. TMEM63B was broadly expressed in DRG neurons, and its global knockout or DRG-specific conditional knockout markedly reduced heat sensitivity. Deletion of TMEM63B significantly attenuated heat-induced calcium responses and currents in DRG neurons and elevated the temperature threshold for action potential initiation. Recombinant TMEM63B exhibited moderate heat response in calcium imaging assays. Notably, in the presence of arachidonic acid, TMEM63B was strongly activated by heat, suggesting that its thermosensitivity is modulated by the membrane lipid environment. Together, these findings identify TMEM63B as a novel channel contributing to heat sensation and reveal a lipid-dependent modulation of its channel activity.
Heat sensation is primarily mediated by thermosensitive channels in mammals, however whether additional channels contribute to noxious heat detection remains unclear. This study shows that the mechanosensitive cation channel TMEM63B contributes to heat sensation through a unique mechanism modulated by the membrane lipid environment.
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BibTeX
@article{ye2026mechanosensitive,
title = {{The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia}},
author = {Chang Ye and Yan-Yu Zang and Gui-Fang Duan and Jiang Chen and Dan Wu and Dan Wang and Changlin Li and Yun Xu and Tianjiao Xia and Xiaoping Gu and Yun Stone Shi},
journal = {PLOS Biology},
year = {2026},
month = oct,
doi = {10.1371/journal.pbio.3004060},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004060},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia
AU - Chang Ye
AU - Yan-Yu Zang
AU - Gui-Fang Duan
AU - Jiang Chen
AU - Dan Wu
AU - Dan Wang
AU - Changlin Li
AU - Yun Xu
AU - Tianjiao Xia
AU - Xiaoping Gu
AU - Yun Stone Shi
PY - 2026
DA - 2026/10/16
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004060
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004060
AB - In mammals, heat sensation is primarily mediated by thermosensitive channels, particularly transient receptor potential (TRP) channels, in dorsal root ganglion (DRG) neurons. However, whether additional channels contribute to noxious heat detection remains unclear. Here, we investigated the role of the mechanosensitive cation channel TMEM63B in DRG neurons and unexpectedly discovered its involvement in noxious thermosensation rather than mechanosensation. TMEM63B was broadly expressed in DRG neurons, and its global knockout or DRG-specific conditional knockout markedly reduced heat sensitivity. Deletion of TMEM63B significantly attenuated heat-induced calcium responses and currents in DRG neurons and elevated the temperature threshold for action potential initiation. Recombinant TMEM63B exhibited moderate heat response in calcium imaging assays. Notably, in the presence of arachidonic acid, TMEM63B was strongly activated by heat, suggesting that its thermosensitivity is modulated by the membrane lipid environment. Together, these findings identify TMEM63B as a novel channel contributing to heat sensation and reveal a lipid-dependent modulation of its channel activity. Heat sensation is primarily mediated by thermosensitive channels in mammals, however whether additional channels contribute to noxious heat detection remains unclear. This study shows that the mechanosensitive cation channel TMEM63B contributes to heat sensation through a unique mechanism modulated by the membrane lipid environment.
SN - 1545-7885
SN - 1544-9173
ER -