10.3389/fncel.2018.00041.s004 Clive P. Morgan Clive P. Morgan Hongyu Zhao Hongyu Zhao Meredith LeMasurier Meredith LeMasurier Wei Xiong Wei Xiong Bifeng Pan Bifeng Pan Piotr Kazmierczak Piotr Kazmierczak Matthew R. Avenarius Matthew R. Avenarius Michael Bateschell Michael Bateschell Ruby Larisch Ruby Larisch Anthony J. Ricci Anthony J. Ricci Ulrich Müller Ulrich Müller Peter G. Barr-Gillespie Peter G. Barr-Gillespie Image_4.tif Frontiers 2018 hair cells stereocilia mechanotransduction TRP channels auditory brainstem response (ABR) 2018-02-20 04:34:40 Figure https://frontiersin.figshare.com/articles/figure/Image_4_tif/5902627 <p>Hair cells of the inner ear transduce mechanical stimuli like sound or head movements into electrical signals, which are propagated to the central nervous system. The hair-cell mechanotransduction channel remains unidentified. We tested whether three transient receptor channel (TRP) family members, TRPV6, TRPM6 and TRPM7, were necessary for transduction. TRPV6 interacted with USH1C (harmonin), a scaffolding protein that participates in transduction. Using a cysteine-substitution knock-in mouse line and methanethiosulfonate (MTS) reagents selective for this allele, we found that inhibition of TRPV6 had no effect on transduction in mouse cochlear hair cells. TRPM6 and TRPM7 each interacted with the tip-link component PCDH15 in cultured eukaryotic cells, which suggested they might be part of the transduction complex. Cochlear hair cell transduction was not affected by manipulations of Mg<sup>2+</sup>, however, which normally perturbs TRPM6 and TRPM7. To definitively examine the role of these two channels in transduction, we showed that deletion of either or both of their genes selectively in hair cells had no effect on auditory function. We suggest that TRPV6, TRPM6 and TRPM7 are unlikely to be the pore-forming subunit of the hair-cell transduction channel.</p>