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DOI: 10.1055/s-0041-1728468
Probing Force Relay in Drosophila melanogaster Hearing
Sensitive hearing in the fruit fly, Drosophila melanogaster, requires the NOMPC (TRPN1) channel [1]. NOMPC is a bona fide mechano-electrical transduction (MET) channel that possesses a domain consisting of 29 ankyrin repeats (ARs). These 29 ARs assemble into a helix [2], tether the channel intracellularly to microtubules [3], and are essential for mechano-gating [3].
Duplicating the NOMPC AR-domain yields in functional NOMPC29+29ARs channels [3]. How this duplication affects the relay of force, to and from the channel, remains unknown. Consistent with previous reports [3], NOMPC29+29ARs enabled mechano-activated currents in heterologous expression systems (Drosophila S2 cell line). The mechanosensitivity of these MET currents resembled those observed when expressing normal NOMPC, as did sensitive hearing when replacing NOMPC in the adult fly with NOMPC29+29ARs.
Strikingly, the NOMPC-dependent nonlinear gating compliance in the fly’s auditory mechanics [1] was found unaffected. Hence, duplicating the NOMPC AR-domain, neither affects NOMPC mechanosensitivity in in vitro nor in vivo. Our analysis suggests that the NOMPC ARs are in series with more compliant elements. Genetic manipulations have narrowed down the identities of these highly compliant elements, which represent an integral component of NOMPC.
[1] Effertz T, et al. (2012). Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1. Nat Neurosci. 15, 1198-1200.
[2] Jin, P. et al. (2017). Electron cryo-microscopy structure of the mechanotransduction channel NOMPC. Nature 547, 118-122.
[3] Zhang, W. et al. (2015). Ankyrin repeats convey force to gate the NOMPC mechanotransduction channel. Cell 162, 1391-1403. Supported by DFG, SFB889, A1.
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Artikel online veröffentlicht:
13. Mai 2021
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