Identification of a new co-factor, MOG1, required for the full function of cardiac sodium channel Nav1.5

Ling Wu, Sandro L. Yong, Chun Fan, Ying Ni, Shin Yoo, Teng Zhang, Xianqin Zhang, Carlos A. Obejero-Paz, Hyun Jin Rho, Tie Ke, Przemyslaw Szafranski, Stephen W. Jones, Qiuyun Chen, Qing Kenneth Wang

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The cardiac sodium channel Nav1.5 is essential for the physiological function of the heart and contributes to lethal cardiac arrhythmias and sudden death when mutated. Here, we report that MOG1, a small protein that is highly conserved from yeast to humans, is a central component of the channel complex and modulates the physiological function of Na v1.5. The yeast two-hybrid screen identified MOG1 as a new protein that interacts with the cytoplasmic loop II (between transmembrane domains DII and DIII) of Nav1.5. The interaction was further demonstrated by both in vitro glutathione S-transferase pull-down and in vivo co-immunoprecipitation assays in both HEK293 cells with co-expression of MOG1 and Nav1.5 and native cardiac cells. Co-expression of MOG1 with Nav1.5 in HEK293 cells increased sodium current densities. In neonatal myocytes, overexpression of MOG1 increased current densities nearly 2-fold. Western blot analysis revealed that MOG1 increased cell surface expression of Nav1.5, which may be the underlying mechanism by which MOG1 increased sodium current densities. Immunostaining revealed that in the heart, MOG1 was expressed in both atrial and ventricular tissues with predominant localization at the intercalated discs. In cardiomyocytes, MOG1 is mostly localized in the cell membrane and co-localized with Nav1.5. These results indicate that MOG1 is a critical regulator of sodium channel function in the heart and reveal a new cellular function for MOG1. This study further demonstrates the functional diversity of Nav1.5-binding proteins, which serve important functions for Nav1.5 under different cellular conditions.

Original languageEnglish (US)
Pages (from-to)6968-6978
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number11
DOIs
StatePublished - Mar 14 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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