PUBLICATION

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

Authors
Erickson, T., Morgan, C.P., Olt, J., Hardy, K., Busch-Nentwich, E.M., Maeda, R., Clemens-Grisham, R., Krey, J.F., Nechiporuk, A.V., Barr-Gillespie, P.G., Marcotti, W., Nicolson, T.
ID
ZDB-PUB-170524-6
Date
2017
Source
eLIFE   6: (Journal)
Registered Authors
Busch-Nentwich, Elisabeth, Clemens-Grisham, Rachel, Erickson, Timothy, Maeda, Reo, Nechiporuk, Alex, Nicolson, Teresa
Keywords
neuroscience, zebrafish
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Hair Cells, Auditory/physiology*
  • Hearing Loss, Sensorineural/genetics*
  • Mechanotransduction, Cellular*
  • Membrane Proteins/metabolism*
  • Methyltransferases*
  • Mutation
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed
28534737 Full text @ Elife
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes