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Amino Acids

, Volume 47, Issue 2, pp 429–434 | Cite as

Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel

  • Pedro Beltran-Alvarez
  • Ferran Feixas
  • Sílvia Osuna
  • Rubí Díaz-Hernández
  • Ramon Brugada
  • Sara Pagans
Short Communication

Abstract

Arginine methylation is a novel post-translational modification within the voltage-gated ion channel superfamily, including the cardiac sodium channel, NaV1.5. We show that NaV1.5 R513 methylation decreases S516 phosphorylation rate by 4 orders of magnitude, the first evidence of protein kinase A inhibition by arginine methylation. Reciprocally, S516 phosphorylation blocks R513 methylation. NaV1.5 p.G514C, associated to cardiac conduction disease, abrogates R513 methylation, while leaving S516 phosphorylation rate unchanged. This is the first report of methylation–phosphorylation cross-talk of a cardiac ion channel.

Keywords

Sodium channel Post-translational modification Arginine methylation Phosphorylation Cross-talk 

Abbreviations

MALDI-TOF

Matrix-assisted laser desorption–ionization time of flight

NaV1.5

Voltage-gated sodium channel, cardiac isoform, α subunit

PKA

cAMP-dependent protein kinase

PRMT

Protein arginine methyltransferase

SAM

S-adenosyl-l-methionine

Notes

Acknowledgments

The clone for expression of PRMT3 as GST fusion was a gift from Alexsandra Espejo and Mark. T. Bedford (MD Anderson Cancer Center). We thank Ariel Escobar (UC Merced), Guillermo Pérez, and Fabiana Scornik (University of Girona) for critical reading of the manuscript. Peptide synthesis was performed by Javier Valle and David Andreu (Laboratory of Proteomics and Protein Chemistry, University Pompeu Fabra, Barcelona). We thank Antonia Odena and Eliandre de Oliveira (Proteomics Platform, University of Barcelona, member of the ProteoRed-ISCIII network), and Guadalupe Espadas, Jenny G. Donoso and Eduard Sabidó (CRG/UPF Proteomics Unit) for help with LC–MS/MS analyses. This work was funded by Fundació Obra Social La Caixa, Spanish Government [SAF2011-27627, CTQ2011-25086/BQU)], and European Community [PCIG14-GA-2013-630978]. PB-A acknowledges a Sara Borrell fellowship [CD10/00275], SO a JdC contract [JCI-2012-14438] and FF a Beatriu de Pinós fellowship [BP-2010-A2_00022].

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

726_2014_1890_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1378 kb)

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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Cardiovascular Genetics Center, Institut d’Investigació Biomèdica de Girona Dr. Josep TruetaUniversity of GironaGironaSpain
  2. 2.Department of Medical Sciences, School of MedicineUniversity of GironaGironaSpain
  3. 3.Institut de Química Computacional i Catàlisi (IQCC) and Departament de QuímicaUniversitat de GironaGironaSpain

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