Zhang Wei, Cheng Li E, Kittelmann Maike, Li Jiefu, Petkovic Maja, Cheng Tong, Jin Peng, Guo Zhenhao, Göpfert Martin C, Jan Lily Yeh, Jan Yuh Nung
Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Cellular Neurobiology, University of Göttingen, 37077 Göttingen, Germany.
Cell. 2015 Sep 10;162(6):1391-403. doi: 10.1016/j.cell.2015.08.024.
How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels.
后生动物的机械转导通道如何感知机械刺激尚不清楚。瞬时受体电位(TRP)家族中的NOMPC通道是果蝇触觉和听觉的机械转导通道,它含有29个与微管相关的锚蛋白重复序列(ARs)。这些ARs被认为起到了将力传递给通道的系链作用。在此,我们报告这些N端ARs形成了一个胞质结构域,该结构域对于体外NOMPC机械门控、体内触觉感受神经元的机械敏感性以及果蝇幼虫的触觉诱导行为至关重要。复制这些ARs会延长将NOMPC系于机械感觉神经元微管上的细丝。此外,微管结合对于NOMPC机械门控是必需的。重要的是,将NOMPC的ARs转移到机械不敏感的电压门控钾通道上会赋予嵌合通道机械敏感性。这些实验有力地支持了NOMPC通道机械门控的系链机制,为机械转导通道机械敏感性的基础提供了见解。