title: Protein arginine methyl transferases-3 and -5 increase cell surface expression of cardiac sodium channel.
abstract: The α-subunit of the cardiac voltage-gated sodium channel (NaV1.5) plays a central role in cardiomyocyte excitability. We have recently reported that NaV1.5 is post-translationally modified by arginine methylation. Here, we aimed to identify the enzymes that methylate NaV1.5, and to describe the role of arginine methylation on NaV1.5 function. Our results show that protein arginine methyl transferase (PRMT)-3 and -5 methylate NaV1.5 in vitro, interact with NaV1.5 in human embryonic kidney (HEK) cells, and increase NaV1.5 current density by enhancing NaV1.5 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.
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain; Institute for Physiology II, University Hospital, 07743 Jena, Germany. Electronic address: pbeltran@idibgi.org.
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltran-Alvarez
authors.forename: Alexsandra
authors.initials: A
authors.lastname: Espejo
authors.forename: Ralf
authors.initials: R
authors.lastname: Schmauder
authors.forename: Carlos
authors.initials: C
authors.lastname: Beltran
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.forename: Thomas
authors.initials: T
authors.lastname: Linke
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.forename: Félix
authors.initials: F
authors.lastname: Pérez-Villa
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Pérez
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Scornik
authors.forename: Klaus
authors.initials: K
authors.lastname: Benndorf
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
authors.forename: Thomas
authors.initials: T
authors.lastname: Zimmer
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C413164:PRMT3 protein, human; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: AP; ArgMe; Arginine methylation; CFP or YFP; FRET; Förster resonance energy transfer; HEK; IP; Ion channel; L(I–II); Na(V)1.5; PRMT; Post-translational modification; S-(5′-adenosyl)-l-methionine; SAM; Sodium channel; action potential; arginine methylation; beats per minute; bmp; cardiac isoform of the voltage-gated sodium channel α subunit; co-IP; co-immunoprecipitation; cyan or yellow fluorescent protein; human embryonic kidney; immunoprecipitation; linker between domains DI and DII of Na(V)1.5; protein arginine methyltransferase