Molecular basis for heat desensitization of TRPV1 ion channels

Lei Luo, Yunfei Wang, Bowen Li, Lizhen Xu, Peter Muiruri Kamau, Jie Zheng, Fan Yang, Shilong Yang, Ren Lai

Research output: Contribution to journalArticle

Abstract

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a prototypical molecular sensor for noxious heat in mammals. Its role in sustained heat response remains poorly understood, because rapid heat-induced desensitization (Dh) follows tightly heat-induced activation (Ah). To understand the physiological role and structural basis of Dh, we carried out a comparative study of TRPV1 channels in mouse (mV1) and those in platypus (pV1), which naturally lacks Dh. Here we show that a temperature-sensitive interaction between the N- and C-terminal domains of mV1 but not pV1 drives a conformational rearrangement in the pore leading to Dh. We further show that knock-in mice expressing pV1 sensed heat normally but suffered scald damages in a hot environment. Our findings suggest that Dh evolved late during evolution as a protective mechanism and a delicate balance between Ah and Dh is crucial for mammals to sense and respond to noxious heat.

Original languageEnglish (US)
Article number2134
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Ion Channels
Hot Temperature
heat
mammals
Mammals
mice
Platypus
vanilloid receptor subtype 1
Chemical activation
activation
damage
porosity
Temperature
sensors
Sensors
interactions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Molecular basis for heat desensitization of TRPV1 ion channels. / Luo, Lei; Wang, Yunfei; Li, Bowen; Xu, Lizhen; Kamau, Peter Muiruri; Zheng, Jie; Yang, Fan; Yang, Shilong; Lai, Ren.

In: Nature communications, Vol. 10, No. 1, 2134, 01.12.2019.

Research output: Contribution to journalArticle

Luo, L, Wang, Y, Li, B, Xu, L, Kamau, PM, Zheng, J, Yang, F, Yang, S & Lai, R 2019, 'Molecular basis for heat desensitization of TRPV1 ion channels', Nature communications, vol. 10, no. 1, 2134. https://doi.org/10.1038/s41467-019-09965-6
Luo, Lei ; Wang, Yunfei ; Li, Bowen ; Xu, Lizhen ; Kamau, Peter Muiruri ; Zheng, Jie ; Yang, Fan ; Yang, Shilong ; Lai, Ren. / Molecular basis for heat desensitization of TRPV1 ion channels. In: Nature communications. 2019 ; Vol. 10, No. 1.
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AU - Zheng, Jie

AU - Yang, Fan

AU - Yang, Shilong

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