Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel

Beltran-Alvarez, Pedro; Feixas, Ferran; Osuna, Sílvia; Díaz-Hernández, Rubí; Brugada, Ramon; Pagans, Sara

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.

Citation

Beltran-Alvarez, P., Feixas, F., Osuna, S., Díaz-Hernández, R., Brugada, R., & Pagans, S. (2015). Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel. Amino acids, 47(2), 429-434. https://doi.org/10.1007/s00726-014-1890-0

• Journal Article Type: Article
• Acceptance Date: Dec 4, 2014
• Online Publication Date: Dec 16, 2014
• Publication Date: 2015-02
• Deposit Date: Mar 11, 2016
• Publicly Available Date: Mar 11, 2016
• Journal: Amino acids
• Print ISSN: 0939-4451
• Electronic ISSN: 1438-2199
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 47
• Issue: 2
• Pages: 429-434
• DOI: https://doi.org/10.1007/s00726-014-1890-0
• Keywords: Sodium channel; Post-translational modification; Arginine methylation; Phosphorylation; Cross-talk
• Public URL: https://hull-repository.worktribe.com/output/412788
• Publisher URL: http://link.springer.com/article/10.1007%2Fs00726-014-1890-0
• Additional Information: Author's accepted manuscript of article published in: Amino acids, 2014, v.47, issue 2. The final publication is available at Springer via http://dx.doi.org/10.1007/s00726-014-1890-0