PMID:23255163

Citation	Molina, L, Fasquelle, L, Nouvian, R, Salvetat, N, Scott, HS, Guipponi, M, Molina, F, Puel, JL and Delprat, B (2013) Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression. Hum. Mol. Genet. 22:1289-99
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 Tmprss3(WT) and Tmprss3(Y260X)-mutant mice. Interestingly, only outward K(+) 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).
Links	PubMed Online version:10.1093/hmg/dds532
Keywords	Animals; Apolipoprotein A-I/genetics; Apolipoprotein A-I/metabolism; Cochlea/cytology; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Gene Expression; Hair Cells, Auditory, Inner/metabolism; Humans; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism; Membrane Potentials; Membrane Proteins/genetics; Membrane Proteins/metabolism; Metabolic Networks and Pathways; Mice; Mice, Transgenic; Mutation, Missense; Patch-Clamp Techniques; Potassium/metabolism; Protein Transport; Proteome/metabolism; Serine Proteases/genetics; Serine Proteases/metabolism; Tandem Mass Spectrometry
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:TMPS3		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Figure 2 shows Tmprss3 positively regulates multiple proteins related to Kcnma1 as shown in red portion of Figure 2B,C.	complete CACAO 13055
MOUSE:TMPS3		GO:0010629: negative regulation of gene expression	ECO:0000315:		P		Figure 2 shows Tmprss3 negatively regulates multiple proteins related to Kcnma1 as shown in green portion of Figure 2B,C.	complete CACAO 13075

References

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