Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression
| Autor: | Jean-Luc Puel, Laurence Molina, Benjamin Delprat, Régis Nouvian, Franck Molina, Hamish S. Scott, Lydie Fasquelle, Nicolas Salvetat, Michel Guipponi |
|---|---|
| Přispěvatelé: | Molina, Laurence, Fasquelle, Lydie, Nouvian, Regis, Salvetat, Nicolas, Scott, Hamish S, Guippponi, Michel, Molina, Franck, Puel, Jean-Luc, Delprat, Benjamin |
| Rok vydání: | 2012 |
| Předmět: |
Patch-Clamp Techniques
Proteome Mutation Missense Down-Regulation Gene Expression Tissue membrane Mice Transgenic Biology Membrane Potentials Mice Auditory Hair Cell Tandem Mass Spectrometry Genetics medicine Animals Humans Electrophoresis Gel Two-Dimensional Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Molecular Biology Genetics (clinical) Cochlea Hair Cells Auditory Inner Apolipoprotein A-I Membrane Proteins General Medicine Anatomy Mice transgenic Protein Transport medicine.anatomical_structure Potassium Hair cell Serine Proteases Metabolic Networks and Pathways |
| Zdroj: | Human Molecular Genetics. 22:1289-1299 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | usc 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 immunohisto chemistry, focusing on the most down regulated 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). Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|