Arginylation regulates myofibrils to maintain heart function and prevent dilated cardiomyopathy

摘要: Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, which deletion was driven α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe contractility defects, dilated cardiomyopathy, thrombosis over time, resulting high rates of lethality after 6months age. symptoms accompanied ultrastructural defects myofibrils, seen newborns far preceding onset suggesting that these primary likely underlay development future defects. Several major sarcomeric proteins arginylated vivo. Moreover, hearts resulted a significant reduction active passive myofibril forces, critical both structural integrity contractility. Thus, maintaining function regulation absence leads to progressive failure through cardiomyocyte-specific