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

Christopher L. Cunningham, Zizhen Wu, Aria Jafari, Bo Zhao, Kat Schrode, Sara Harkins-Perry, Amanda Lauer, Ulrich Müller

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere24318
JournaleLife
Volume6
DOIs
StatePublished - May 15 2017
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

Fingerprint

Dive into the research topics of 'The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells'. Together they form a unique fingerprint.

Cite this