4.7 Article

Glutamine Regulates Cell Growth and Casein Synthesis through the CYTHs/ARFGAP1-Arf1-mTORC1 Pathway in Bovine Mammary Epithelial Cells

期刊

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 24, 页码 6810-6819

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c02223

关键词

glutamine; milk protein synthesis; ADP-ribosylation factor 1; ADP-ribosylation factor GTPase activating protein 1; Cytohesin-1/2/3; mTORC1 pathway; bovine mammary epithelial cells

资金

  1. China Postdoctoral Science Foundation [2019M662971]
  2. Guangdong Basic and Applied Basic Research Foundation [2018A030313392]
  3. Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01S131]

向作者/读者索取更多资源

This study demonstrates that glutamine (Gln) positively regulates cell growth and casein synthesis in bovine mammary epithelial cells (BMECs) through the CYTHs/ARFGAP1-Arf1-mTORC1 pathway, providing new insights into the regulation of the mTOR pathway by amino acids.
In the dairy industry, glutamine (Gln) is often used as a feed additive to increase milk yield and quality; however, the molecular regulation underneath needs further clarification. Here, with bovine mammary epithelial cells (BMECs), the effects and mechanisms of Gln on cell growth and casein synthesis were assessed. When Gln was added or depleted from BMECs, both cell growth and beta-casein (CSN2) expression were increased or decreased, respectively. Overexpressing or inhibiting the mechanistic target of rapamycin (mTOR) revealed that Gln regulated cell growth and CSN2 synthesis through the mTORC1 pathway. A similar intervention of ADP-ribosylation factor 1 (Arf1) uncovered that Gln activated the mTORC1 pathway through Arf1. We next observed that both guanine nucleotide exchange factors, Cytohesin-1/2/3 (CYTH1/2/3, CYTHs) and ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1), interacted with Arf1. Inhibiting CYTHs or ARFGAP1 showed that Gln supplement or depletion activated or inactivated Arf1 through CYTHs or ARFGAP1, respectively. Collectively, this study demonstrated that Gln positively regulated cell growth and casein synthesis in BMECs, which works through the CYTHs/ARFGAP1-Arf1-mTORC1 pathway. These results greatly enhanced current understanding regarding the regulation of the mTOR pathway and provided new insights for the processes of cell growth and casein synthesis by amino acids, particularly Gln.

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