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J Mol Cell Cardiol. 2014 Nov;76:126-9. doi: 10.1016/j.yjmcc.2014.08.014. Epub 2014 Aug 27.

Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart.

Author information

1
Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, 17003 Girona, Spain. Electronic address: pbeltran@idibgi.org.
2
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.
3
Proteomics Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
4
Thorax Institute, Cardiology Department, Hospital Clínic, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer, 08036 Barcelona, Spain.
5
Logopharm GmbH, 79232 March-Buchheim, Germany.
6
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.
7
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.

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.

KEYWORDS:

Arginine methylation; Heart failure; N-terminal acetylation; Post-translational modification; Proteomics; Voltage-gated sodium channel

PMID:
25172307
DOI:
10.1016/j.yjmcc.2014.08.014
[Indexed for MEDLINE]

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