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Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function
Parveen Sharma1, Cynthia Abbasi1, Savo Lazic2
1Department of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
Nature Communications
|September 26, 2015
Summary
The membrane protein Tmem65 is vital for heart development and function. It regulates connexin 43 (Cx43) localization and gap junction function in cardiac intercalated discs.
Area of Science:
- Cardiovascular Biology
- Membrane Protein Research
- Developmental Biology
Background:
- Membrane proteins are essential for cardiac function and development.
- Understanding cardiac-specific membrane proteins is crucial for identifying novel therapeutic targets.
Purpose of the Study:
- To identify and characterize novel plasma membrane-associated proteins in cardiomyocytes.
- To investigate the role of Tmem65 in cardiac development and function.
Main Methods:
- Cationic silica-bead coating combined with shotgun proteomics for protein enrichment.
- In vitro knockdown using lentiviral shRNA in mouse cardiomyocytes.
- In vivo knockdown using morpholino in zebrafish.
Main Results:
- Tmem65 identified as a cardiac-enriched protein localized to intercalated discs, increasing with development.
- Tmem65 knockdown in vitro and in vivo caused altered gap junction function and cardiac morphology.
- Tmem65 interacts with connexin 43 (Cx43), regulating its localization, stability, and function.
Conclusions:
- Tmem65 is a key intercalated disc protein regulating Cx43 in ventricular cardiomyocytes.
- Tmem65 plays a critical role in maintaining cardiac structure and function.
- Tmem65 represents a potential therapeutic target for cardiac diseases.
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