PUBLICATION
Subunits of the mechano-electrical transduction channel, Tmc1/2b, require Tmie to localize in zebrafish sensory hair cells
- Authors
- Pacentine, I.V., Nicolson, T.
- ID
- ZDB-PUB-190207-10
- Date
- 2019
- Source
- PLoS Genetics 15: e1007635 (Journal)
- Registered Authors
- Nicolson, Teresa, Pacentine, Itallia
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Membrane Structures/metabolism
- Deafness/metabolism
- Hair Cells, Auditory/metabolism*
- Hearing Loss, Sensorineural/metabolism
- Mechanotransduction, Cellular/physiology
- Membrane Proteins/metabolism*
- Mutation/physiology
- Stereocilia/metabolism
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 30726219 Full text @ PLoS Genet.
Citation
Pacentine, I.V., Nicolson, T. (2019) Subunits of the mechano-electrical transduction channel, Tmc1/2b, require Tmie to localize in zebrafish sensory hair cells. PLoS Genetics. 15:e1007635.
Abstract
Mutations in transmembrane inner ear (TMIE) cause deafness in humans; previous studies suggest involvement in the mechano-electrical transduction (MET) complex in sensory hair cells, but TMIE's precise role is unclear. In tmie zebrafish mutants, we observed that GFP-tagged Tmc1 and Tmc2b, which are subunits of the MET channel, fail to target to the hair bundle. In contrast, overexpression of Tmie strongly enhances the targeting of Tmc1-GFP and Tmc2b-GFP to stereocilia. To identify the motifs of Tmie underlying the regulation of the Tmcs, we systematically deleted or replaced peptide segments. We then assessed localization and functional rescue of each mutated/chimeric form of Tmie in tmie mutants. We determined that the first putative helix was dispensable and identified a novel critical region of Tmie, the extracellular region and transmembrane domain, which is required for both mechanosensitivity and Tmc2b-GFP expression in bundles. Collectively, our results suggest that Tmie's role in sensory hair cells is to target and stabilize Tmc channel subunits to the site of MET.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping