Research Article

E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator

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Science  21 Dec 2018:
Vol. 362, Issue 6421, eaan3303
DOI: 10.1126/science.aan3303

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Protecting the heart

Excitation-contraction (E-C) coupling is fundamental to heart contraction. Junctophilin-2 is a structural protein required for formation of the E-C coupling machinery. During heart disease, stress-activated calpain cleaves junctophilin-2, disrupting the E-C coupling machinery and calcium ion signaling, which compromises cell contraction. Guo et al. found that under stress conditions, calpain-mediated cleavage converted full-length junctophilin-2 from a structural protein into a transcriptional regulator that shuttled to the nucleus (see the Perspective by Padmanabhan and Haldar). Furthermore, failing cardiomyocytes in stressed myocardium transduced mechanical information (E-C uncoupling) into transcriptional reprogramming.

Science, this issue p. eaan3303; see also p. 1359

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