title: Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation.
abstract: Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The association between hnRNP M and Rictor was verified using recombinant and endogenous protein and the binding site was found to be within aa 1~532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKCα S657 and PKCζ T560. Furthermore, hnRNP M also plays a critical role in muscle differentiation because knock-down of either hnRNP M or Rictor in C2C12 myoblasts reduced differentiation. This decrease is able to be rescued by overexpression SGK S422D in hnRNP M knockdown C2C12 myoblasts. Taken together, we have identified a novel Rictor/mTOR binding molecule, hnRNP M, that allows mTORC2 signaling to phosphorylate SGK1 thus regulating muscle differentiation.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Wei-Yen
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Jen-Hua
authors.initials: JH
authors.lastname: Chuang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Chiu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Yun-Ya
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
authors.forename: Mei-Chih
authors.initials: MC
authors.lastname: Liang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
authors.forename: Yenshou
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D000076226:Rapamycin-Insensitive Companion of mTOR Protein / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; D017874:Immediate-Early Proteins; D051571:Protein Kinase C-alpha; D017346:Protein Serine-Threonine Kinases; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000099184:Serum-Glucocorticoid Regulated Kinases; C525637:rictor protein, mouse; C496630:Prkca protein, mouse