title: Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart.
abstract: The α subunit of the cardiac voltage-gated sodium channel, NaV1.5, provides the rapid sodium inward current that initiates cardiomyocyte action potentials. Here, we analyzed for the first time the post-translational modifications of NaV1.5 purified from end-stage heart failure human cardiac tissue. We identified R526 methylation as the major post-translational modification of any NaV1.5 arginine or lysine residue. Unexpectedly, we found that the N terminus of NaV1.5 was: 1) devoid of the initiation methionine, and 2) acetylated at the resulting initial alanine residue. This is the first evidence for N-terminal acetylation in any member of the voltage-gated ion channel superfamily. Our results open the door to explore NaV1.5 N-terminal acetylation and arginine methylation levels as drivers or markers of end-stage heart failure.
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain. Electronic address: pbeltran@idibgi.org.
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltran-Alvarez
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Tarradas
authors.affiliation: Proteomics Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Chiva
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pérez-Serra
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clínic, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clínic, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Pérez-Villa
authors.affiliation: Logopharm GmbH, 79232 March-Buchheim, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulte
authors.affiliation: Proteomics Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Sabidó
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain. Electronic address: rbrugada@idibgi.org.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain. Electronic address: sara.pagans@udg.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D001120:Arginine
keywords: Arginine methylation; Heart failure; N-terminal acetylation; Post-translational modification; Proteomics; Voltage-gated sodium channel