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Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel

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
Cell 2015 v.162 pp. 1391-1403
Drosophila, chimerism, hearing, larvae, mechanotransduction, microtubules, neurons, potassium channels, touch (sensation), transient receptor potential channels
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.