Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation

Wei Yen Chen, Chia Lung Lin, Jen Hua Chuang, Fu Yu Chiu, Yun Ya Sun, Mei Chih Liang, Yenshou Lin

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number41159
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017 Jan 20

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Heterogeneous-Nuclear Ribonucleoprotein Group M
Muscles
Sirolimus
Myoblasts
S 657
1-(3-trifluoromethylphenyl)-2-(N-(2-hydroxyethyl)amino)propane
TOR complex 2
Immunoprecipitation
Recombinant Proteins
Protein Binding
Mass Spectrometry
Cell Survival

ASJC Scopus subject areas

  • General

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Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation. / Chen, Wei Yen; Lin, Chia Lung; Chuang, Jen Hua; Chiu, Fu Yu; Sun, Yun Ya; Liang, Mei Chih; Lin, Yenshou.

In: Scientific Reports, Vol. 7, 41159, 20.01.2017.

Research output: Contribution to journalArticle

Chen, Wei Yen ; Lin, Chia Lung ; Chuang, Jen Hua ; Chiu, Fu Yu ; Sun, Yun Ya ; Liang, Mei Chih ; Lin, Yenshou. / Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation. In: Scientific Reports. 2017 ; Vol. 7.
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