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Identification of a New Co-factor, MOG1, Required for the Full Function of Cardiac Sodium Channel Nav1.5
- Source :
- Journal of Biological Chemistry. 283:6968-6978
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- The cardiac sodium channel Nav 1.5 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 Nav 1.5. 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 Nav 1.5. 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.
- Subjects :
- Muscle Proteins
Nav1.5
Models, Biological
Biochemistry
Sudden death
Sodium Channels
NAV1.5 Voltage-Gated Sodium Channel
Cell membrane
Mice
Western blot
Two-Hybrid System Techniques
medicine
Animals
Humans
Myocyte
Molecular Biology
Glutathione Transferase
medicine.diagnostic_test
biology
Sodium channel
HEK 293 cells
Heart
Cell Biology
Molecular biology
Cell biology
Electrophysiology
Transmembrane domain
ran GTP-Binding Protein
medicine.anatomical_structure
Animals, Newborn
Gene Expression Regulation
Mice, Inbred CBA
biology.protein
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 283
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....2ad4d15af53e923fe06263f750b4b8dc