E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator-Reference-Cited by-同舟云学术

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

Published:2018-12-21 Issue:6421 Volume:362 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Guo Ang¹^ORCID,Wang Yihui¹²,Chen Biyi¹,Wang Yunhao¹,Yuan Jinxiang¹,Zhang Liyang³,Hall Duane¹^ORCID,Wu Jennifer¹,Shi Yun¹,Zhu Qi¹⁴^ORCID,Chen Cheng¹²,Thiel William H.¹,Zhan Xin¹^ORCID,Weiss Robert M.¹,Zhan Fenghuang¹,Musselman Catherine A.³,Pufall Miles³^ORCID,Zhu Weizhong⁴,Au Kin Fai¹^ORCID,Hong Jiang²^ORCID,Anderson Mark E.⁵,Grueter Chad E.¹⁶,Song Long-Sheng¹⁶⁷^ORCID

Affiliation:

1. Department of Internal Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.

2. Department of Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

3. Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.

4. Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu 226001, China.

5. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.

6. Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.

7. Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.

Abstract

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

Funder

National Heart, Lung, and Blood Institute

U.S. Department of Veterans Affairs

American Heart Association

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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