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

Beltran-Alvarez, Pedro; Tarradas, Anna; Chiva, Cristina; Pérez-Serra, Alexandra; Batlle, Montserrat; Pérez-Villa, Félix; Schulte, Uwe; Sabidó, Eduard; Brugada, Ramon; Pagans, Sara

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.

Citation

Beltran-Alvarez, P., Tarradas, A., Chiva, C., Pérez-Serra, A., Batlle, M., Pérez-Villa, F., …Pagans, S. (2014). Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart. Journal of Molecular and Cellular Cardiology, 76, 126-129. https://doi.org/10.1016/j.yjmcc.2014.08.014

• Acceptance Date: Aug 15, 2014
• Online Publication Date: Aug 27, 2014
• Publication Date: Nov 1, 2014
• Deposit Date: Mar 10, 2016
• Publicly Available Date: Oct 27, 2022
• Journal: Journal of molecular and cellular cardiology
• Print ISSN: 0022-2828
• Electronic ISSN: 1095-8584
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 76
• Pages: 126-129
• DOI: https://doi.org/10.1016/j.yjmcc.2014.08.014
• Keywords: Voltage-gated sodium channel, Proteomics, Post-translational modification, N-terminal acetylation, Arginine methylation, Heart failure
• Public URL: https://hull-repository.worktribe.com/output/412671
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0022282814002612
• Additional Information: Author's accepted manuscript of article published in: Journal of molecular and cellular cardiology, 2014, v.76