Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program
Authors: Jared Rutter
Steven P Gygi
Seong Anthony Woo Kang
Chintan K Kikani
Xiaoying Wu
David M Sabatini
Noah Dephoure
Sarah Fogarty
Journal: Proceedings of the National Academy of Sciences of the United States of America (2019)
Discipline: Multidisciplinary
Keywords: PASK; Pax7; mTOR; muscle stem cell; myogenin.
Affiliations: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132;  ., Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132., Whitehead Institute for Biomedical Research, Cambridge, MA 02142., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142., Department of Cell Biology, Harvard Medical School, Boston, MA 02115., Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139., Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142., Broad Institute of Harvard and MIT, Cambridge, MA 02142., Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84132.

Abstract:  During skeletal muscle regeneration, muscle stem cells (MuSCs) respond to multiple signaling inputs that converge onto mammalian target of rapamycin complex 1 (mTORC1) signaling pathways. mTOR function is essential for establishment of the differentiation-committed progenitors (early stage of differentiation, marked by the induction of myogenin expression), myotube fusion, and, ultimately, hypertrophy (later stage of differentiation). While a major mTORC1 substrate, p70S6K, is required for myotube fusion and hypertrophy, an mTORC1 effector for the induction of myogenin expression remains unclear. Here, we identified Per-Arnt-Sim domain kinase (PASK) as a downstream phosphorylation target of mTORC1 in MuSCs during differentiation. We have recently shown that the PASK phosphorylates Wdr5 to stimulate MuSC differentiation by epigenetically activating the myogenin promoter. We show that phosphorylation of PASK by mTORC1 is required for the activation of myogenin transcription, exit from self-renewal, and induction of the myogenesis program. Our studies reveal that mTORC1-PASK signaling is required for the rise of myogenin-positive committed myoblasts (early stage of myogenesis), whereas mTORC1-S6K signaling is required for myoblast fusion (later stage of myogenesis). Thus, our discoveries allow molecular dissection of mTOR functions during different stages of the myogenesis program driven by two different substrates. 

Retracted: No

PubPeer comments:
 1-tAuthor claims that reference [49] contains knowledge about the involvement of secondary metabolites specifically Flavonoid, proteins, gallic acid, and terpenoids from the plant (*O. Sanctum*) extract. But in reality, if you will explore this referred article, there is nothing about these mentioned metabolites. 2-tSimilarly, Authors explain that reference [54] is about the use of secondary metabolites Flavonoids, proteins, amino acids, amides and terpenoids from the *H. annuus* plant extract. But in actual, this referred article does not provide any knowledge about the mentioned metabolites. 3-tIn reference [70] to [72], author claims that these research articles explains the role of Catechins, and hydroxyflavone from the plant extracts for the synthesis of nanoparticles. But in reality, there is no information found in the quoted articles about the relevant secondary metabolites. 4-tIn the current review author quoted that the article under reference no [111] explains synthesis of Au nanoparticles using *Tamarindus indica* plant extract. Amazingly if you will explore reference no [111], it has nothing to do with nanoparticles or even nanoscience. Article under reference no [111] is about u201ceffects of different levels of sodium hypochlorite (1u20134 g 100 g dry solids active chlorine) on the physicochemical, pasting, and structural properties of tamarind kernel starchesu201d. 5-tIn short, information quoted in connection with articles under reference no [47], [59], [63], [67, [68], [75], [76], [77], [81], [84], [87], [90], [98], [105], [106], [108], [109], [112], [117], [118], [119], [137], and [138] is also not true. , 
 Correction published [8 March 2019] . ----------------------------------------- The authors have overlooked a few mistakes when rearranging the Tables 1 and 2 and references at the final stages, which were carried-over to the published version of the review. Consequently the authors wish to make at this time the following corrections to the paper [1]: ![file] Page 11, final paragraph: Citation [208] should be read as [218]. **References** 70. Geethalakshmi, R.; Sarada, D.V. Synthesis of plant-mediated silver nanoparticles using Trianthema decandra extract and evaluation of their antimicrobial activities. Int. J. Eng. Sci. Technol. 2010, 2, 970u2013975. 111. Correa, S.N.; Naranjo, A.M.; Herrera; A.P. Biosynthesis and characterization of gold nanoparticles using extracts of Tamarindus indica L Leaves. J. Phys.: Conf. Ser. 2016, 687, 012082. 225. Shah, M.; Fawcett, D.; Sharma, S.; Tripathy, S.K.; Poinern, G.E.J. Green synthesis of metallic nanoparticles via biological entities. Materials 2015, 8, 7278u20137308. The manuscript will be updated and the original will remain available on the article webpage. We would like to apologize for any inconvenience caused to the readers. ,