Protein arginine methyl transferases‐3 and ‐5 increase cell surface expression of cardiac sodium channel. Issue 19 (31st July 2013)

• Record Type: Journal Article
• Authors: Beltran-Alvarez, Pedro; Espejo, Alexsandra; Schmauder, Ralf; Beltran, Carlos; Mrowka, Ralf; Linke, Thomas; Batlle, Montserrat; Pérez-Villa, Félix; Pérez, Guillermo J.; Scornik, Fabiana S.; Benndorf, Klaus; Pagans, Sara; Zimmer, Thomas; Brugada, Ramon
• Is Part Of: FEBS letters. Volume 587:Issue 19(2013)
• Page Start: 3159
• Page End: 3165
• Publication Date: 2013-07-31
• Subjects: AP -- action potential -- ArgMe -- arginine methylation -- bmp -- beats per minute -- CFP or YFP -- cyan or yellow fluorescent protein -- co-IP -- co-immunoprecipitation -- FRET -- Förster resonance energy transfer -- HEK -- human embryonic kidney -- IP -- immunoprecipitation -- LI–II -- linker between domains DI and DII of NaV1.5 -- NaV1.5 -- cardiac isoform of the voltage-gated sodium channel α subunit -- PRMT -- protein arginine methyltransferase -- SAM -- S-(5′-adenosyl)-l-methionine -- Arginine methylation -- Ion channel -- Post-translational modification -- Sodium channel; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.07.043
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The α‐subunit of the cardiac voltage‐gated sodium channel (NaV 1.5) plays a central role in cardiomyocyte excitability. We have recently reported that NaV 1.5 is post‐translationally modified by arginine methylation. Here, we aimed to identify the enzymes that methylate NaV 1.5, and to describe the role of arginine methylation on NaV 1.5 function. Our results show that protein arginine methyl transferase (PRMT)‐3 and ‐5 methylate NaV 1.5 in vitro, interact with NaV 1.5 in human embryonic kidney (HEK) cells, and increase NaV 1.5 current density by enhancing NaV 1.5 cell surface expression. Our observations are the first evidence of regulation of a voltage‐gated ion channel, including calcium, potassium, sodium and TRP channels, by arginine methylation. Abstract : We identify the protein arginine methyl transferases (PRMT) that methylate NaV 1.5. We describe the effect of PRMT on NaV 1.5 function. PRMT3 and PRMT5 increase NaV 1.5 cell surface expression. This is the first report showing that PRMT regulate a voltage‐gated ion channel.