Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783242530982199296 |
---|---|
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 |
format | Online Article Text |
id | pubmed-5462538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cunninghamchristopherl themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT wuzizhen themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT jafariaria themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT zhaobo themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT schrodekat themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT harkinsperrysarah themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT laueramanda themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT mullerulrich themurinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT cunninghamchristopherl murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT wuzizhen murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT jafariaria murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT zhaobo murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT schrodekat murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT harkinsperrysarah murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT laueramanda murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells AT mullerulrich murinecatecholaminemethyltransferasemtomtisessentialformechanotransductionbycochlearhaircells |