The β4 Subunit of L-Type Ca2+ Channels Regulates Transcription of Antiviral Factors in a Heart Cell Line

Abstract

Integrator 1 (BIN1), in the clustering of Ca v 1.2 channels in ventricular myocytes. Both of these proteins are known to directly interact with Ca v 1.2 channels. AKAP150 is important for local membrane targeting of PKA, PKCa and calcineurin, while Bin1 has established roles in cardiac t-tubule folding and in the trafficking and localization of Ca v 1.2 channels to t-tubules. Using GSD superresolution imaging, we found that clustering of Ca v 1.2 channels in these cells is unaltered by genetic ablation of AKAP79/150 such that the area of Ca V 1.2 clusters was similar in WT (2379 5 43 nm) and AKAP150 -/myocytes (2379 5 43 nm). However, heterozygous deletion of Bin1 significantly reduced Ca v 1.2 channel cluster size. The area of Ca V 1.2 channel clusters was approximately 42% smaller in BIN1 þ/-(1379 5 43 nm) than in WT (2349 5 76 nm 2 ) ventricular myocytes (p< 0.0001). This data suggests that Bin1 is a key regulator of Ca v 1.2 channel clustering in heart.

The β 4 subunit of Ca v 1.2 channels is required for an optimal interferon response in cardiac muscle cells

“…We previously showed that these cells are susceptible to infection by dengue virus (DENV) (23), a single-stranded positive RNA virus of the Flaviviridae family, the pathogenic agent that causes dengue fever, which can damage the heart, liver, lungs, and other organs and is potentially fatal (24)(25)(26). Previous work showed that Ca 2+ homeostasis is disturbed by viral proteins (27,28). Furthermore, increased [Ca 2+ ] i has been observed in skeletal muscle cells from DENV-infected patients (25), and critical virus-host interactions depend on cellular Ca 2+ -regulated proteins; however, the involvement of Ca v 1.2 channels in viral infection of the heart is unclear.…”