Hehlert Philip, Effertz Thomas, Gu Ruo-Xu, Nadrowski Björn, Geurten Bart R H, Beutner Dirk, de Groot Bert L, Göpfert Martin C
Department of Cellular Neurobiology, University of Göttingen, Göttingen, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Nat Neurosci. 2025 Feb;28(2):259-267. doi: 10.1038/s41593-024-01849-3. Epub 2025 Jan 6.
The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the Drosophila mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate. This linker acts as a Hookean hinge that is ten times more elastic than the tether, with the linker hinge dictating channel gating and the intrinsic stiffness of the gating spring. Our study shows how mechanosensation is initiated molecularly; disentangles gating springs and tethers, and respective paradigms of channel gating; and puts forward gating springs as core ion channel constituents that enable efficient gating by diverse stimuli and in a wide variety of channels.
机械刺激的感觉是由弹性门控弹簧启动的，这些弹簧拉开机械感觉转导通道。对门控弹簧的研究集中在力传递蛋白系链上，如果蝇机械感觉转导通道NOMPC的氨基末端锚蛋白系链。在这里，通过将蛋白质结构域重复与力学测量、电生理学、分子动力学模拟和建模相结合，我们确定NOMPC门控弹簧是锚蛋白系链和通道门之间的短连接子。这个连接子充当胡克铰链，其弹性比系链大十倍，连接子铰链决定通道门控和门控弹簧的固有刚度。我们的研究展示了机械感觉在分子层面是如何启动的；解开了门控弹簧和系链以及通道门控的各自模式；并提出门控弹簧是核心离子通道成分，能够通过多种刺激在各种各样的通道中实现高效门控。
