Mechanistic insights into the interaction of the MOG1 protein with the cardiac sodium channel Na_v1.5 clarify the molecular basis of Brugada syndrome.

ABSTRACT: Na_v1.5 is the α-subunit of the cardiac sodium channel complex. Abnormal expression of Na_v1.5 on the cell surface because of mutations that disrupt Na_v1.5 trafficking causes Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction disease, dilated cardiomyopathy, and sudden infant death syndrome. We and others previously reported that Ran-binding protein MOG1 (MOG1), a small protein that interacts with Na_v1.5, promotes Na_v1.5 intracellular trafficking to plasma membranes and that a substitution in MOG1, E83D, causes BrS. However, the molecular basis for the MOG1/Nav1.5 interaction and how the E83D substitution causes BrS remains unknown. Here, we assessed the effects of defined MOG1 deletions and alanine-scanning substituti

SUBMITTER: Yu G 

PROVIDER: S-EPMC6254340 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature