Key result
LITAF controls cardiac excitability by promoting degradation of NEDD4-2, increasing Nav1.5 surface protein levels and sodium current, which explains its association with QT interval variation.
Why the study?
Genetic variants upstream of the endosomal trafficking regulator LITAF were known to modify the QT interval, but how LITAF impacts cardiac excitation remained unclear.
Population
Rabbit cardiomyocytes, HEK cells stably expressing Nav1.5, and LITAF-knockout zebrafish
Comparison
LITAF overexpression or knockout vs controls
Design
Preclinical in vitro, in vivo, and computational study
Authors
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LITAF-NEDD4-2 axis may modulate QT in models; leaves open whether targeting alters human arrhythmia risk.
LITAF regulates cardiac excitability by promoting the degradation of NEDD4-2, thereby increasing Nav1.5 surface levels and sodium current, providing a mechanistic basis for its association with QT interval variation.
Turan et al. (2020) studied QT interval variation. LITAF overexpression or knockout was evaluated on Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels. LITAF controls cardiac excitability by promoting degradation of NEDD4-2, increasing Nav1.5 surface protein levels and sodium current, which explains its association with QT interval variation.
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