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Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.
- Source :
- Nature medicine; vol 20, iss 6, 624-632; 1078-8956
- Publication Year :
- 2014
-
Abstract
- Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is downregulated in failing hearts. Here we find that cardiac T tubules normally contain dense protective inner membrane folds that are formed by a cardiac isoform of BIN1. In mice with cardiac Bin1 deletion, T-tubule folding is decreased, which does not change overall cardiomyocyte morphology but leads to free diffusion of local extracellular calcium and potassium ions, prolonging action-potential duration and increasing susceptibility to ventricular arrhythmias. We also found that T-tubule inner folds are rescued by expression of the BIN1 isoform BIN1+13+17, which promotes N-WASP-dependent actin polymerization to stabilize the T-tubule membrane at cardiac Z discs. BIN1+13+17 recruits actin to fold the T-tubule membrane, creating a 'fuzzy space' that protectively restricts ion flux. When the amount of the BIN1+13+17 isoform is decreased, as occurs in acquired cardiomyopathy, T-tubule morphology is altered, and arrhythmia can result.
Details
- Database :
- OAIster
- Journal :
- Nature medicine; vol 20, iss 6, 624-632; 1078-8956
- Notes :
- Hong, TingTing, Yang, Huanghe, Zhang, Shan-Shan, Cho, Hee Cheol, Kalashnikova, Mariya, Sun, Baiming, Zhang, Hao, Bhargava, Anamika, Grabe, Michael, Olgin, Jeffrey, Gorelik, Julia, Marbán, Eduardo, Jan, Lily Y, Shaw, Robin M
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1367463296
- Document Type :
- Electronic Resource