Work

Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program

Year: 2019

Type: article

Abstract: Significance Skeletal muscle harbors a robust, yet quiescent stem cell population. These stem cells are activated upon myofiber injury to repair damaged myotome. This regenerative myogenesis is guided by external signaling cues that allow stem cells to acquire various stem cell fates. Here, we describe a growth factor and nutrient-stimulated pathway, whereby mammalian target of rapamycin (mTOR) activates Per–Arnt–Sim domain kinase (PASK) protein kinase in muscle stem cells. This mTOR-dependent activation of PASK is required for the transcriptional induction of the myogenin gene and subsequent terminal differentiation program. Finally, our results suggest that mTOR-PASK and mTOR-S6 Kinase signaling are required for distinct stages of myogenesis program, and link nutrient environment to early stages of the myogenesis program.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1804013116