The cardiac sodium channel is post-translationally modified by arginine methylation.
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Beltran-Alvarez P, Pagans S, Brugada R
The cardiac sodium channel is post-translationally modified by arginine methylation.
J Proteome Res. 2011 Aug 5;10(8):3712-9. doi: 10.1021/pr200339n. Epub 2011 Jul 18.
- PubMed ID
- 21726068 [ View in PubMed]
- Abstract
The alpha subunit of the cardiac sodium channel (Na(v)1.5) is an essential protein in the initial depolarization phase of the cardiomyocyte action potential. Post-translational modifications such as phosphorylation are known to regulate Na(v)1.5 function. Here, we used a proteomic approach for the study of the post-translational modifications of Na(v)1.5 using tsA201 cells as a model system. We generated a stable cell line expressing Na(v)1.5, purified the sodium channel, and analyzed Na(v)1.5 by MALDI-TOF and LC-MS/MS. We report the identification of arginine methylation as a novel post-translational modification of Na(v)1.5. R513, R526, and R680, located in the linker between domains I and II in Na(v)1.5, were found in mono- or dimethylated states. The functional relevance of arginine methylation in Na(v)1.5 is underscored by the fact that R526H and R680H are known Na(v)1.5 mutations causing Brugada and long QT type 3 syndromes, respectively. Our work describes for the first time arginine methylation in the voltage-gated ion channel superfamily.