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Type: Journal article
Title: Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression
Author: Molina, L.
Fasquelle, L.
Nouvian, R.
Salvetat, N.
Scott, H.
Guipponi, M.
Molina, F.
Puel, J.
Delprat, B.
Citation: Human Molecular Genetics, 2013; 22(7):1289-1299
Publisher: Oxford Univ Press
Issue Date: 2013
ISSN: 0964-6906
Statement of
Laurence Molina, Lydie Fasquelle, Régis Nouvian, Nicolas Salvetat, Hamish S. Scott, Michel Guipponi, Franck Molina, Jean-Luc Puel and Benjamin Delprat
Abstract: Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K+ currents, we compared their function by patch-clamp technique in wild-type Tmprss3WT and Tmprss3Y260X-mutant mice. Interestingly, only outward K+ currents were altered in Tmprss3Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3WT and Tmprss3Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3WT, Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs).
Keywords: Cochlea
Mice, Transgenic
Apolipoprotein A-I
Membrane Proteins
Electrophoresis, Gel, Two-Dimensional
Patch-Clamp Techniques
Gene Expression
Membrane Potentials
Protein Transport
Mutation, Missense
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Tandem Mass Spectrometry
Metabolic Networks and Pathways
Hair Cells, Auditory, Inner
Serine Proteases
Rights: © The Author 2012. Published by Oxford University Press. All rights reserved.
DOI: 10.1093/hmg/dds532
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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