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

ELife
Christopher CunninghamUlrich Mueller

Abstract

Hair cells of the cochlea are mechanosensors for the perception of sound. Mutations in theLRTOMTgene, which encodes a protein with homology to the catecholamine methyltransferase COMT that is linked to schizophrenia, cause deafness. Here, we show thatTomt/Comt2, the murine ortholog ofLRTOMT, 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 inLRTOMT/Tomt.

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Citations

Aug 30, 2017·Cold Spring Harbor Perspectives in Biology·Avinash JaiganeshMarcos Sotomayor
Aug 8, 2018·Cold Spring Harbor Perspectives in Medicine·Christopher L Cunningham, Ulrich Müller
Oct 7, 2018·Cold Spring Harbor Perspectives in Medicine·David P CoreyJeffrey R Holt
Oct 5, 2019·Cellular and Molecular Life Sciences : CMLS·Xiaomin YueRui Xiao
Jan 13, 2019·Journal of the Association for Research in Otolaryngology : JARO·Sarah B Pickett, David W Raible
Dec 15, 2020·Scientific Reports·Pankhuri VyasHakim Hiel
Apr 20, 2021·Cellular and Molecular Life Sciences : CMLS·Shuang LiuWei Xiong

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
PCR
genetic modifications
scanning electron microscopy
co-immunoprecipitation
CoIP
SANS
in
in vitro transcription
transfection
transfect

Software Mentioned

Empower
mTOMT
Igor pro
Patchmaster
mCOMT
HEKA
Excel
TDT
TDT System

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