▎ACHIEVEMENTS

It has been found that a mutation of the sarcomeric proteins causes an abnormality in sarcomere assembly that induces cardiomyopathy. Composed of hundreds of sarcomeric proteins, sarcomere is the fundamental functional unit of heart muscle. The mechanism of sarcomere assembly in the early stages of heart development remains unclear. Researchers must understand this mechanism in order to devise effective treatments of cardiomyopathy.

The research team led by Associate Prof. Su-Yi Tsai, Department of Life Science, National Taiwan University, developed a new system that reveals the expression of core sarcomere-related proteins in a temporal and spatial manner during the differentiation of human pluripotent stem cells into cardiomyocytes, disclosing the molecular mechanism of sarcomere assembly.

The research team also found that the molecular chaperon UNC45B has high-level coexpression with sarcomere marker proteins in different components of the sarcomere structure, and investigated whether UNC45B plays different roles in these different components. Notably, they found that UNC45B-deficient cardiomyocytes do not contract. However, their mechanism studies revealed that UNC45B regulates the formation of protocostamere, the starting point of sarcomere assembly, by regulating the expression of KINDLIN2. Importantly, the research team confirmed that UNC45B regulates the formation of cardiac sarcomeres by interacting with sarcomere-associated proteins in different components of the sarcormore structure in a spatiotemporal manner.

These findings are of crucial importance because expectant mothers with UNC45B mutations may give birth to babies with neonatal myofibrillar myopathy type II, which cannot survive long after birth. The findings of this study open the way to devising new treatment strategies for neonatal myofibrillar myopathy type II.