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The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells.

eLife | May 15, 2017

Hair cells of the cochlea are mechanosensors for the perception of sound. Mutations in the LRTOMT gene, which encodes a protein with homology to the catecholamine methyltransferase COMT that is linked to schizophrenia, cause deafness. Here, we show that Tomt/Comt2, the murine ortholog of LRTOMT, has an unexpected function in the regulation of mechanotransduction by hair cells. The role of mTOMT in hair cells is independent of mTOMT methyltransferase function and mCOMT cannot substitute for mTOMT function. Instead, mTOMT binds to putative components of the mechanotransduction channel in hair cells and is essential for the transport of some of these components into the mechanically sensitive stereocilia of hair cells. Our studies thus suggest functional diversification between mCOMT and mTOMT, where mTOMT is critical for the assembly of the mechanotransduction machinery of hair cells. Defects in this process are likely mechanistically linked to deafness caused by mutations in LRTOMT/Tomt.

Pubmed ID: 28504928 RIS Download

Mesh terms: Animals | Catechol O-Methyltransferase | Catecholamines | Hair Cells, Auditory | Mechanotransduction, Cellular | Methylation | Mice

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Associated grants

  • Agency: NIDCD NIH HHS, Id: F32 DC015724
  • Agency: NIDCD NIH HHS, Id: P30 DC005211
  • Agency: NIDCD NIH HHS, Id: R01 DC005965

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