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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

Authors

Profile image of Pedro Beltran-Alvarez

Dr Pedro Beltran-Alvarez P.Beltran-Alvarez@hull.ac.uk
Senior Lecturer in Health and Climate Change and Programme co-Director of the MSc Health and Climate Change

Anna Tarradas

Cristina Chiva

Alexandra Pérez-Serra

Montserrat Batlle

Félix Pérez-Villa

Uwe Schulte

Eduard Sabidó

Ramon Brugada

Sara Pagans



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., Schulte, U., Sabidó, E., Brugada, R., & 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 Mar 10, 2016
Journal Journal of molecular and cellular cardiology
Print ISSN 0022-2828
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
Contract Date Mar 10, 2016

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