Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond
Authors:Shin-Haw Lee1,2, Sina Hadipour-Lakmehsari1,2 and Anthony O. Gramolini1,2
1 Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada M5G1M1.
2 Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S1M8.
Keywords:
SR organization, cardiac myocytes, cardiac ER stress, zebrafish, heart function, heart development.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Shin-Haw Lee, Sina Hadipour-Lakmehsari and Anthony O. Gramolini (2020). Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond. Cell Stress 4(6): 151-153. doi: 10.15698/cst2020.06.223
© 2020 Lee et al. This is an open-access article released under the terms of the Creative Commons At-tribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, pro-vided the original author and source are acknowledged.
Abstract:
The sarco-endoplasmic reticulum (SR/ER) is the largest membrane-bound organelle in eukaryotic cells and plays important roles in essential cellular processes, and in development and progression of many cardiac diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. In a recently published study led by Lee et al. (Nat Commun 11(1):965), we reported 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 resulted 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 showed sensitized cardiac dysfunction to heart failure induction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrated cardiac dysfunction with dilated cardiac chambers, increased cardiac fibrosis, and reduced ejection fraction. These results demonstrate the critical role of REEP5 in SR/ER organization and function.