Proteomic analyses reveal GNG12 regulates cell growth and casein synthesis by activating the Leu-mediated mTORC1 signaling pathway

文献类型： 外文期刊

第一作者： Luo, Chaochao

作者： Luo, Chaochao;Zhao, Shengguo;Dai, Wenting;Zheng, Nan;Wang, Jiaqi;Luo, Chaochao;Zhao, Shengguo;Dai, Wenting;Zheng, Nan;Wang, Jiaqi;Luo, Chaochao;Zhao, Shengguo;Dai, Wenting;Zheng, Nan;Wang, Jiaqi

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关键词： Proteomics; GNG12; Cow mammary epithelial cells; mTORC1 pathway; Casein synthesis; SWATH mass spectrometry

期刊名称：BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS （ 影响因子：3.036； 五年影响因子：2.969 ）

ISSN： 1570-9639

年卷期： 2018 年 1866 卷 11 期

页码：

收录情况： SCI

摘要： In cow mammary epithelial cells (CMECs), cell growth and casein synthesis are regulated by amino acids (AAs), and lysosomes are important organelles in this regulatory process, but the mechanisms remain unclear. Herein, lysosomal membrane proteins (LMPs) in CMECs in the presence (Leu +) and absence (Leu-) of leucine were quantitatively analysed using Sequential Windowed Acquisition of All Theoretical Fragment Ion (SWATH) mass spectrometry. In identified LMPs, Guanine nucleotide-binding protein subunit gamma-12 (GNG12) was a markedly up-regulated protein in Leu+ group. CMECs were treated with Leu+ or Leu, expression and lysosomal localization of GNG12 were decreased in response to Leu absence. Overexpressing or inhibiting GNG12 demonstrated that cell growth, casein synthesis and activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway were all up-regulated by GNG12. Cell growth, casein synthesis and mTORC1 signaling pathway were decreased in response to Leo absence, but these decreases were partially restored by GNG12 overexpression, and those effects were partially reversed by inhibiting GNG12. Co-immunoprecipitation analysis showed that GNG12 activates the mTORC1 pathway via interaction with Ragulator. Taken together, these results suggest that GNG12 is a positive regulator of the Leu-mediated mTORC1 signaling pathway in CMECs that promotes cell growth and casein synthesis.

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