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

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...

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Autores principales: Cunningham, Christopher L, Wu, Zizhen, Jafari, Aria, Zhao, Bo, Schrode, Kat, Harkins-Perry, Sarah, Lauer, Amanda, Müller, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462538/
https://www.ncbi.nlm.nih.gov/pubmed/28504928
http://dx.doi.org/10.7554/eLife.24318
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author Cunningham, Christopher L
Wu, Zizhen
Jafari, Aria
Zhao, Bo
Schrode, Kat
Harkins-Perry, Sarah
Lauer, Amanda
Müller, Ulrich
author_facet Cunningham, Christopher L
Wu, Zizhen
Jafari, Aria
Zhao, Bo
Schrode, Kat
Harkins-Perry, Sarah
Lauer, Amanda
Müller, Ulrich
author_sort Cunningham, Christopher L
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.24318.001
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spelling pubmed-54625382017-06-09 The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells Cunningham, Christopher L Wu, Zizhen Jafari, Aria Zhao, Bo Schrode, Kat Harkins-Perry, Sarah Lauer, Amanda Müller, Ulrich eLife Neuroscience 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. DOI: http://dx.doi.org/10.7554/eLife.24318.001 eLife Sciences Publications, Ltd 2017-05-15 /pmc/articles/PMC5462538/ /pubmed/28504928 http://dx.doi.org/10.7554/eLife.24318 Text en © 2017, Cunningham et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Cunningham, Christopher L
Wu, Zizhen
Jafari, Aria
Zhao, Bo
Schrode, Kat
Harkins-Perry, Sarah
Lauer, Amanda
Müller, Ulrich
The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title_full The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title_fullStr The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title_full_unstemmed The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title_short The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells
title_sort murine catecholamine methyltransferase mtomt is essential for mechanotransduction by cochlear hair cells
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462538/
https://www.ncbi.nlm.nih.gov/pubmed/28504928
http://dx.doi.org/10.7554/eLife.24318
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