Molina, L.Fasquelle, L.Nouvian, R.Salvetat, N.Scott, H.Guipponi, M.Molina, F.Puel, J.Delprat, B.2013-08-302013-08-302013Human Molecular Genetics, 2013; 22(7):1289-12990964-69061460-2083http://hdl.handle.net/2440/79653Before 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).en© The Author 2012. Published by Oxford University Press. All rights reserved.CochleaAnimalsMice, TransgenicHumansMicePotassiumApolipoprotein A-IMembrane ProteinsProteomeElectrophoresis, Gel, Two-DimensionalPatch-Clamp TechniquesGene ExpressionDown-RegulationMembrane PotentialsProtein TransportMutation, MissenseLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsTandem Mass SpectrometryMetabolic Networks and PathwaysHair Cells, Auditory, InnerSerine ProteasesJournal article002012652810.1093/hmg/dds5320003162970000032-s2.0-8487523863020640Scott, H. [0000-0002-5813-631X]