Proteomic analyses reveal GNG12 regulates cell growth and casein synthesis by activating the Leu-mediated mTORC1 signaling pathway |
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| Institution: | 1. State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China;2. Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China;3. Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China;1. Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics (CDFD), Inner Ring Road, Uppal, Hyderabad 500039, Telangana, India;2. Department of Medical Genetics, Nizam''s Institute of Medical Sciences, Punjagutta, Hyderabad 500082, Telangana, India;1. School of Veterinary Science, College of Life, Environment, and Advanced Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai Kita, Izumisano, Osaka 598-8531, Japan;2. Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai Kita, Izumisano, Osaka 598-8531, Japan;1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA;2. Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA;1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia;2. Novosibirsk State University, Novosibirsk, Russia |
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| Abstract: | 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 Leu 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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