title: The cardiac sodium channel is post-translationally modified by arginine methylation.
abstract: The α 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.
authors: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, Hospital Dr. Josep Trueta, Girona, Spain.
authors: Pedro
authors: P
authors: Beltran-Alvarez
authors: Sara
authors: S
authors: Pagans
authors: Ramon
authors: R
authors: Brugada
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002853:Chromatography, Liquid; D017931:DNA Primers; D008745:Methylation; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D017931:DNA Primers; D015222:Sodium Channels; D001120:Arginine