Title: Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation
Authors: Chen, Wei-Yen
Lin, Chia-Lung
Chuang, Jen-Hua
Chiu, Fu-Yu
Sun, Yun-Ya
Liang, Mei-Chih
Lin, Yenshou
Department of Biological Science and Technology
Issue Date: 20-Jan-2017
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 similar to 532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKC alpha S657 and PKC zeta 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.
URI: http://dx.doi.org/10.1038/srep41159
ISSN: 2045-2322
DOI: 10.1038/srep41159
Volume: 7
Appears in Collections:Articles