TRPV6, TRPM6 and TRPM7 do not contribute to hair-cell mechanotransduction

Clive P. Morgan, Hongyu Zhao, Meredith LeMasurier, Wei Xiong, Bifeng Pan, Piotr Kazmierczak, Matthew R. Avenarius, Michael Bateschell, Ruby Larisch, Anthony J. Ricci, Ulrich Müller, Peter Barr-Gillespie

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 Mg2+, 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.

Original languageEnglish (US)
Article number41
JournalFrontiers in Cellular Neuroscience
Volume12
DOIs
StatePublished - Feb 20 2018

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Hair
Auditory Hair Cells
Head Movements
Eukaryotic Cells
Inner Ear
Cysteine
Cultured Cells
Central Nervous System
Alleles
Genes
Proteins

Keywords

  • Auditory brainstem response (ABR)
  • Hair cells
  • Mechanotransduction
  • Stereocilia
  • TRP channels

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

TRPV6, TRPM6 and TRPM7 do not contribute to hair-cell mechanotransduction. / Morgan, Clive P.; Zhao, Hongyu; LeMasurier, Meredith; Xiong, Wei; Pan, Bifeng; Kazmierczak, Piotr; Avenarius, Matthew R.; Bateschell, Michael; Larisch, Ruby; Ricci, Anthony J.; Müller, Ulrich; Barr-Gillespie, Peter.

In: Frontiers in Cellular Neuroscience, Vol. 12, 41, 20.02.2018.

Research output: Contribution to journalArticle

Morgan, CP, Zhao, H, LeMasurier, M, Xiong, W, Pan, B, Kazmierczak, P, Avenarius, MR, Bateschell, M, Larisch, R, Ricci, AJ, Müller, U & Barr-Gillespie, P 2018, 'TRPV6, TRPM6 and TRPM7 do not contribute to hair-cell mechanotransduction', Frontiers in Cellular Neuroscience, vol. 12, 41. https://doi.org/10.3389/fncel.2018.00041
Morgan, Clive P. ; Zhao, Hongyu ; LeMasurier, Meredith ; Xiong, Wei ; Pan, Bifeng ; Kazmierczak, Piotr ; Avenarius, Matthew R. ; Bateschell, Michael ; Larisch, Ruby ; Ricci, Anthony J. ; Müller, Ulrich ; Barr-Gillespie, Peter. / TRPV6, TRPM6 and TRPM7 do not contribute to hair-cell mechanotransduction. In: Frontiers in Cellular Neuroscience. 2018 ; Vol. 12.
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