REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects



Lee, Shin-Haw, Hadipour-Lakmehsari, Sina, Murthy, Harsha R, Gibb, Natalie, Miyake, Tetsuaki, Teng, Allen CT, Cosme, Jake, Yu, Jessica C, Moon, Mark, Lim, SangHyun
et al (show 9 more authors) (2020) REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects. NATURE COMMUNICATIONS, 11.

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Abstract

The sarco-endoplasmic reticulum (SR/ER) plays an important role in the development and progression of many heart diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. Here, we report a cardiac enriched, SR/ER membrane protein, REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes. In vitro REEP5 depletion in mouse cardiac myocytes results in SR/ER membrane destabilization and luminal vacuolization along with decreased myocyte contractility and disrupted Ca2+ cycling. Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants show sensitized cardiac dysfunction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrates cardiac dysfunction. These results demonstrate the critical role of REEP5 in SR/ER organization and function as well as normal heart function and development.

Item Type: Article
Uncontrolled Keywords: cell biology, developmental biology, organelles
Depositing User: Symplectic Admin
Date Deposited: 12 Mar 2020 08:32
Last Modified: 10 Sep 2022 08:24
DOI: 10.1038/s41467-019-14143-9
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3078719