Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt)

Timothy Erickson; Clive P. Morgan; Jennifer Olt; Katherine Hardy; Elisabeth Busch-Nentwich; Reo Maeda; Rachel Clemens; Jocelyn F. Krey; Alex Nechiporuk; Peter G. Barr-Gillespie; Walter Marcotti; Teresa Nicolson

doi:10.7554/eLife.28474

Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt)

Timothy Erickson, Clive P. Morgan, Jennifer Olt, Katherine Hardy, Elisabeth Busch-Nentwich, Reo Maeda, Rachel Clemens, Jocelyn F. Krey, Alex Nechiporuk, Peter G. Barr-Gillespie, Walter Marcotti, Teresa Nicolson

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non- syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP- tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle.

Original language	English (US)
Article number	e28474
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.28474
State	Published - May 23 2017

ASJC Scopus subject areas

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

Access to Document

10.7554/eLife.28474

Cite this

Erickson, T., Morgan, C. P., Olt, J., Hardy, K., Busch-Nentwich, E., Maeda, R., Clemens, R., Krey, J. F., Nechiporuk, A., Barr-Gillespie, P. G., Marcotti, W., & Nicolson, T. (2017). Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt). eLife, 6, Article e28474. https://doi.org/10.7554/eLife.28474

@article{9083404e5a7c48998549aac8c6cc3aaf,

title = "Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt)",

abstract = "Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non- syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP- tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle.",

author = "Timothy Erickson and Morgan, {Clive P.} and Jennifer Olt and Katherine Hardy and Elisabeth Busch-Nentwich and Reo Maeda and Rachel Clemens and Krey, {Jocelyn F.} and Alex Nechiporuk and Barr-Gillespie, {Peter G.} and Walter Marcotti and Teresa Nicolson",

note = "Publisher Copyright: {\textcopyright} Erickson et al.",

year = "2017",

month = may,

day = "23",

doi = "10.7554/eLife.28474",

language = "English (US)",

volume = "6",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt)

AU - Erickson, Timothy

AU - Morgan, Clive P.

AU - Olt, Jennifer

AU - Hardy, Katherine

AU - Busch-Nentwich, Elisabeth

AU - Maeda, Reo

AU - Clemens, Rachel

AU - Krey, Jocelyn F.

AU - Nechiporuk, Alex

AU - Barr-Gillespie, Peter G.

AU - Marcotti, Walter

AU - Nicolson, Teresa

PY - 2017/5/23

Y1 - 2017/5/23

N2 - Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non- syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP- tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle.

AB - Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non- syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP- tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle.

UR - http://www.scopus.com/inward/record.url?scp=85020788883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020788883&partnerID=8YFLogxK

U2 - 10.7554/eLife.28474

DO - 10.7554/eLife.28474

M3 - Article

C2 - 28534737

AN - SCOPUS:85020788883

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e28474

ER -

Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by transmembrane o-methyltransferase (Tomt)

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this