Protein arginylation, a global biological regulator that targets actin cytoskeleton and the muscle

Abstract

Posttranslational addition of Arg to proteins, mediated by arginyltransferase ATE1 has been first observed in 1963 and remained poorly understood for decades since its original discovery. Recent work demonstrated the global nature of arginylation and its essential role in multiple physiological pathways during embryogenesis and adulthood and identified over a hundred of proteins arginylated in vivo. Among these proteins, the prominent role belongs to the actin cytoskeleton and the muscle, and follow up studies strongly suggests that arginylation constitutes a novel biological regulator of contractility. This review presents an overview of the studies of protein arginylation that led to the discovery of its major role in the muscle.

Keywords: actin; arginylation; muscle.

Figure 1

Major biological pathways regulated by arginylation.

Figure 2

Knockout of arginyltransferase ATE1 leads to major defects in the heart muscle. Electron micrographs of wild type (WT) and ATE1 knockout (KO) muscle show diffuse Z-bands, irreglar sarcomere lengths, and overall disintegration of the cardiac myofibrils, leading to dilated cardiomyopathy and heart failure. See [78] for further details.