Understanding the molecular mechanisms of arrhythmogenic right ventricular cardiomyopathy caused by TMEM43 p.S358L mutation ...

• Main Author: Porter, Zachary G.
• Format: Text
• Language: English
• Published: Memorial University of Newfoundland 2024
• Subjects: Newfoundland
• Online Access: https://dx.doi.org/10.48336/q6ga-ht87; https://research.library.mun.ca/15891/

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by fibrofatty infiltration of the myocardium, life-threatening arrhythmias, and sudden cardiac death. Newfoundland and Labrador is home to a substantial founder population with an autosomal dominant mutation in the transmembrane protein 43 (TMEM43) gene (c.1073C>T; p.S358L), responsible for ARVC type 5. Although we know that this mutation causes ARVC, there is limited information on the TMEM43 protein life cycle, protein-protein interactions, and function. Additionally, it is unknown how the p.S358L mutation affects TMEM43 function, contributes to ARVC, or why it affects only the heart despite being widely expressed. Here I investigate the intracellular trafficking of wild-type TMEM43 in human induced pluripotent stem cells (iPSCs) and iPSC-cardiomyocytes (iPSC-CMs). I find that TMEM43 resides primarily in early endosomes in iPSCs. Interestingly, although TMEM43 remains localized to early endosomes in early ...