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http://purl.uniprot.org/citations/30251687http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30251687http://www.w3.org/2000/01/rdf-schema#comment"

Background

The cardiac sodium channel Nav1.5 is essential for the physiological function of the heart and causes cardiac arrhythmias and sudden death when mutated. Many disease-causing mutations in Nav1.5 cause defects in protein trafficking, a cellular process critical to the targeting of Nav1.5 to cell surface. However, the molecular mechanisms underlying the trafficking of Nav1.5, in particular, the exit from the endoplasmic reticulum (ER) for cell surface trafficking, remain poorly understood.

Methods and results

Here we investigated the role of the SAR1 GTPases in trafficking of Nav1.5. Overexpression of dominant-negative mutant SAR1A (T39N or H79G) or SAR1B (T39N or H79G) significantly reduces the expression level of Nav1.5 on cell surface, and decreases the peak sodium current density (INa) in HEK/Nav1.5 cells and neonatal rat cardiomyocytes. Simultaneous knockdown of SAR1A and SAR1B expression by siRNAs significantly reduces the INa density, whereas single knockdown of either SAR1A or SAR1B has minimal effect. Computer modeling showed that the three-dimensional structure of SAR1 is similar to RAN. RAN was reported to interact with MOG1, a small protein involved in regulation of the ER exit of Nav1.5. Co-immunoprecipitation showed that SAR1A or SAR1B interacted with MOG1. Interestingly, knockdown of SAR1A and SAR1B expression abolished the MOG1-mediated increases in both cell surface trafficking of Nav1.5 and the density of INa.

Conclusions

These data suggest that SAR1A and SAR1B are the critical regulators of trafficking of Nav1.5. Moreover, SAR1A and SAR1B interact with MOG1, and are required for MOG1-mediated cell surface expression and function of Nav1.5."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.org/dc/terms/identifier"doi:10.1016/j.bbadis.2018.09.003"xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Chakrabarti S."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Chen Q."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Huang Y."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Hu Y."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Li S."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Liu S."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Xiong H."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Tang B."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Wang Z."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Wang F."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Xu C."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Wu Q."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Yu G."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Cheng C."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Karnik S.S."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Aridor M."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/author"Wang Q.K."xsd:string
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30251687http://purl.uniprot.org/core/name"Biochim Biophys Acta Mol Basis Dis"xsd:string
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