title: Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel.
abstract: Arginine methylation is a novel post-translational modification within the voltage-gated ion channel superfamily, including the cardiac sodium channel, NaV1.5. We show that NaV1.5 R513 methylation decreases S516 phosphorylation rate by 4 orders of magnitude, the first evidence of protein kinase A inhibition by arginine methylation. Reciprocally, S516 phosphorylation blocks R513 methylation. NaV1.5 p.G514C, associated to cardiac conduction disease, abrogates R513 methylation, while leaving S516 phosphorylation rate unchanged. This is the first report of methylation-phosphorylation cross-talk of a cardiac ion channel.
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta, University of Girona, 17003, Girona, Spain, pbeltran@idibgi.org.
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltran-Alvarez
authors.forename: Ferran
authors.initials: F
authors.lastname: Feixas
authors.forename: Sílvia
authors.initials: S
authors.lastname: Osuna
authors.forename: Rubí
authors.initials: R
authors.lastname: Díaz-Hernández
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
mesh_terms: D006801:Humans; D008745:Methylation; D009206:Myocardium / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human