Probing Force Relay in Drosophila 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 an amino-terminal domain consisting of 29 ankyrin repeats (ARs). These 29 ARs assemble into a helical structure [[2]], tether the channel to microtubules [[3]], and are essential for mechano-gating [[3]].

Duplicating the AR-domain yields functional NOMPC29+29ARs channels [[3]]. How this duplication affects the relay of force, to and from the channel, remained 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 in adult flies only expressing NOMPC29+29ARs.

Strikingly, the NOMPC-dependent nonlinear gating compliance in the fly’s auditory mechanics [[1]] was also found unaffected. Hence, duplicating the AR-domain, neither affects NOMPC mechanosensitivity in vitro nor in vivo.

Our analysis suggests that the ARs are in series with more compliant elements whose deformation promotes mechano-gating. Genetic manipulations have narrowed down the identities of these highly compliant elements, which represent an integral component of NOMPC.

Poster-PDF A-1497.PDF

DFG, SFB889, A1.

• References

• 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.

Publikationsverlauf

Artikel online veröffentlicht:
10. Juni 2020