TMC6作为一种类似于GPCR的受体,通过Gαq信号传输来感知有害的热量
Chen Zhang1, Fang Tong1, Bin Zhou1
1Shanghai Stomatological Hospital & School of Stomatology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Fudan University, Shanghai, China.
Cell discovery
|June 17, 2024
概括
跨膜通道类6 (TMC6) 作为一种类似于G蛋白合受体 (GPCR) 的分子来检测有害的热量. 缺少TMC6会影响热感,但不会影响其他感官感知.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 感官生理学 感官生理学
背景情况:
- 热感应对于生物的生存和适应至关重要.
- 热感应背后的精确分子机制,特别是有害热,仍然不完全理解.
- 一种膜蛋白质的跨膜通道类6 (TMC6) 在背部根结节神经元 (DRG) 中高度表达.
研究的目的:
- 阐明TMC6在感官感知中的功能.
- 研究TMC6在热传感中的作用,特别是有害热检测.
- 为了确定TMC6调解热感的信号通路.
主要方法:
- 产生和分析TMC6缺乏的小鼠,以评估感官感知.
- 通过蛋白相互作用试验和多破坏,研究了TMC6与Gαq的相互作用.
- 利用基于细胞的测试 (HEK293T) 和初级DRG神经元培养来研究细胞内释放和动作潜能发射.
- 采用了Gαq的遗传切除和Gαq结合的GPCR信号通路 (PLC,IP3R) 的药理抑制.
主要成果:
- 缺少TMC6的小鼠在有害的热感中表现出显著的损害,但保留了正常的寒冷,温暖,触摸和机械疼痛感知.
- TMC6通过其C端区域与Gαq相互作用,作为Gαq结合的GPCR类受体起作用.
- 有害的热刺激诱导了TMC6表达细胞内细胞内从内细胞网膜 (ER) 释放,这取决于Gαq/PLC/IP3R信号传递,在TMC6切除或途径抑制时减少.
结论:
- TMC6直接作为一种与Gαq合的类似GPCR的受体,用于感知有害热量.
- TMC6-Gαq信号通路通过细胞内释放来调解有害热的检测.
- 这些发现揭示了一种涉及TMC6.6的新型热感应机制.
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