Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart.
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.
['Beltran-Alvarez|Pedro|P|', 'Tarradas|Anna|A|', 'Chiva|Cristina|C|', 'Pérez-Serra|Alexandra|A|', 'Batlle|Montserrat|M|', 'Pérez-Villa|Félix|F|', 'Schulte|Uwe|U|', 'Sabidó|Eduard|E|', 'Brugada|Ramon|R|', 'Pagans|Sara|S|']
D000107:Acetylation D000595:Amino Acid Sequence D001120:Arginine D002311:Cardiomyopathy, Dilated D006333:Heart Failure D006801:Humans D008745:Methylation D017202:Myocardial Ischemia D009206:Myocardium D062554:NAV1.5 Voltage-Gated Sodium Channel D011499:Protein Processing, Post-Translational
Arginine methylation Voltage-gated sodium channel Heart failure Post-translational modification N-terminal acetylation Proteomics