论文题目: | Molecular Basis for Heat Desensitization of TRPV1 ion Channels |
作者: | Luo L, Wang Y, Li B, Xu L, Kamau PM, Zheng J, Yang F, Yang S, Lai R |
联系作者: | rlai@mail.kiz.ac.cn |
发表年度: | 2019 |
DOI: | doi: 10.1038/s41467-019-09965-6. |
摘要: |
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 |
刊物名称: | Nature Communications |
论文出处: | https://www.nature.com/articles/s41467-019-09965-6 |
影响因子: | 12.353(2017年) |