title: Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel.
abstract: 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.
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Li E
authors.initials: LE
authors.lastname: Cheng
authors.affiliation: Department of Cellular Neurobiology, University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Kittelmann
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jiefu
authors.initials: J
authors.lastname: Li
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Petkovic
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Cellular Neurobiology, University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Göpfert
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
authors.affiliation: Departments of Physiology, Biochemistry, and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: yuhnung.jan@ucsf.edu.
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
mesh_terms: D000818:Animals; D004330:Drosophila / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D008870:Microtubules / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014110:Touch; D050051:Transient Receptor Potential Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D051663:Kv1.2 Potassium Channel; C405783:NOMPC protein, Drosophila; D050051:Transient Receptor Potential Channels