Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression

Laurence Molina, Lydie Fasquelle, Régis Nouvian, Nicolas Salvetat, Hamish S. Scott, Michel Guipponi, Franck Molina, Jean-Luc Puel, Benjamin Delprat
2012 Human Molecular Genetics  
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 1 currents, we compared their function by patch-clamp technique in wild-type Tmprss3 WT and Tmprss3 Y260X -mutant mice.
more » ... y, only outward K 1 currents were altered in Tmprss3 Y260X -mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3 WT and Tmprss3 Y260X -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 Tmprss3 WT , Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3 Y260X -mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs).
doi:10.1093/hmg/dds532 pmid:23255163 fatcat:uub6kysmlfaxhidqyoiqrf77am