PUBLICATION
REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects
- Authors
- Lee, S.H., Hadipour-Lakmehsari, S., Murthy, H.R., Gibb, N., Miyake, T., Teng, A.C.T., Cosme, J., Yu, J.C., Moon, M., Lim, S., Wong, V., Liu, P., Billia, F., Fernandez-Gonzalez, R., Stagljar, I., Sharma, P., Kislinger, T., Scott, I.C., Gramolini, A.O.
- ID
- ZDB-PUB-200222-3
- Date
- 2020
- Source
- Nature communications 11: 965 (Journal)
- Registered Authors
- Gibb, Natalie, Liu, Peter H., Murthy, Harsha, Scott, Ian
- Keywords
- none
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Cells, Cultured
- Endoplasmic Reticulum Stress
- Gene Knockout Techniques
- Gene Silencing
- Heart/growth & development
- Heart/physiopathology*
- Heart Diseases/metabolism
- Heart Diseases/pathology
- Heart Diseases/physiopathology
- Humans
- Intracellular Membranes/metabolism
- Intracellular Membranes/pathology
- Membrane Proteins/deficiency*
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Mice
- Myocardial Contraction
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/physiology
- Sarcoplasmic Reticulum/genetics
- Sarcoplasmic Reticulum/metabolism
- Sarcoplasmic Reticulum/pathology*
- Zebrafish
- PubMed
- 32075961 Full text @ Nat. Commun.
Citation
Lee, S.H., Hadipour-Lakmehsari, S., Murthy, H.R., Gibb, N., Miyake, T., Teng, A.C.T., Cosme, J., Yu, J.C., Moon, M., Lim, S., Wong, V., Liu, P., Billia, F., Fernandez-Gonzalez, R., Stagljar, I., Sharma, P., Kislinger, T., Scott, I.C., Gramolini, A.O. (2020) REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects. Nature communications. 11:965.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping