GCN2和mTORC1信号路径对动物机体氨基酸平衡的调节作用

doi:10.11843/j.issn.0366-6964.2017.09.001

Abstract

Abstract:

Amino acid (AA) balance is of importance to the health and growth of mammals, and GCN2 and mTORC1 signaling pathways play crucial roles in maintaining AA balance in body. GCN2 signaling pathway can effectively sense intracellular AA starvation, mTORC1 signaling pathway can respond to the change of extracellular AA level. Combining with the recent studies regarding GCN2 and mTORC1, this review summarized characteristics of the GCN2 and mTORC1 signaling pathways and the related response mechanism under the condition of AA starvation and sufficiency, e.g. protein synthesis, refusing to feed, an increase of AA transporter, AA synthase expressions and autophagy initiation, etc.. Understanding the regulatory mechanism by which cellular AA balance is kept under different AA nutrition status contributes to the nutritional regulating of nitrogen for animals, thus improving animal gut health.

CLC Number:

S852.2

SHEN Jun-hua, ZHU Wei-yun. Regulation of GCN2 and mTORC1 Signaling Pathways on Amino Acid Balance in Animal Body[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(9): 1565-1571.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://www.xmsyxb.com/EN/10.11843/j.issn.0366-6964.2017.09.001

https://www.xmsyxb.com/EN/Y2017/V48/I9/1565

References

[1] WU G Y. Functional amino acids in nutrition and health[J]. Amino Acids, 2013, 45(3):407-411.
[2] LIU J, YU K F, ZHU W Y. Amino acid sensing in the gut and its mediation in gut-brain signal transduction[J]. Anim Nutr, 2016, 2(2):69-73.
[3] PULENDRAN B. The varieties of immunological experience:of pathogens, stress, and dendritic cells[J]. Annu Rev Immunol, 2015, 33:563-606.
[4] GALLINETTI J, HARPUTLUGIL E, MITCHELL J R. Amino acid sensing in dietary-restriction-mediated longevity:roles of signal-transducing kinases GCN2 and TOR[J]. Biochem J, 2013, 449(1):1-10.
[5] 何流琴, 周锡红, 李铁军, 等. 氨基酸信号对mTOR和GCN2通路的影响研究进展[J]. 生命科学, 2016, 28(11):1398-1404.
HE L Q, ZHOU X H, LI T J, et al. Amino acids signaling study on mTOR and GCN2 pathways[J]. Chinese Bulletin of Life Sciences, 2016, 28(11):1398-1404. (in Chinese)
[6] KONTUREK S J, KONTUREK J W, PAWLIK T, et al. Brain-gut axis and its role in the control of food intake[J]. J Physiol Pharmacol, 2004, 55(1Pt 2):137-154.
[7] SAM A H, TROKE R C, TAN T M, et al. The role of the gut/brain axis in modulating food intake[J]. Neuropharmacology, 2012, 63(1):46-56.
[8] HUBER L, DE LANGE C F M, ERNST C W, et al. Impact of improving dietary amino acid balance for lactating sows on efficiency of dietary amino acid utilization and transcript abundance of genes encoding lysine transporters in mammary tissue[J]. J Anim Sci, 2016, 94(11):4654-4665.
[9] PIPER M D W, SOULTOUKIS G A, BLANC E, et al. Matching dietary amino acid balance to the in silico-translated exome optimizes growth and reproduction without cost to lifespan[J]. Cell Metab, 2017, 25(3):610-621.
[10] EFEYAN A, COMB W C, SABATINI D M. Nutrient-sensing mechanisms and pathways[J]. Nature, 2015, 517(7534):302-310.
[11] PEACOCK J R, WALVOORD R R, CHANG A Y, et al. Amino acid-dependent stability of the acyl linkage in aminoacyl-tRNA[J]. RNA, 2014, 20(6):758-764.
[12] ZABORSKE J M, NARASIMHAN J, JIANG L, et al. Genome-wide analysis of tRNA charging and activation of the eIF2 kinase Gcn2p[J]. J Biol Chem, 2009, 284(37):25254-25267.
[13] LAGEIX S, ZHANG J W, ROTHENBURG S, et al. Interaction between the tRNA-binding and C-terminal domains of yeast Gcn2 regulates kinase activity in vivo[J]. PLoS Genet, 2015, 11(2):e1004991.
[14] CARRARO V, MAURIN A C, LAMBERT-LANGLAIS S, et al. Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2α/ATF4 Pathway[J]. PLoS One, 2010, 5(12):e15716.
[15] FOUGERAY S, MAMI I, BERTHO G, et al. Tryptophan depletion and the kinase GCN2 mediate IFN-γ-induced autophagy[J]. J Immunol, 2012, 189(6):2954-2964.
[16] PAREKH P. Cloning of wheat germ eukaryotic initiation factor eIF2[D]. Austin:University of Texas at Austin, 2009.
[17] SHIN B S, KIM J R, WALKER S E, et al. Initiation factor eIF2γ promotes eIF2-GTP-Met-tRNA_i^Met ternary complex binding to the 40S ribosome[J]. Nat Struct Mol Biol, 2011, 18(11):1227-1234.
[18] VATTEM K M, WEK R C. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells[J]. Proc Natl Acad Sci USA, 2004, 101(31):11269-11274.
[19] CHAVEROUX C, CARRARO V, CANAPLE L, et al. In vivo imaging of the spatiotemporal activity of the eIF2α-ATF4 signaling pathway:Insights into stress and related disorders[J]. Sci Signal, 2015, 8(374):rs5.
[20] TIMOSENKO E, GHADBANE H, SILK J D, et al. Nutritional stress induced by tryptophan-degrading enzymes results in ATF4-dependent reprogramming of the amino acid transporter profile in tumor cells[J]. Cancer Res, 2016, 76(21):6193-6204.
[21] BALASUBRAMANIAN M N, BUTTERWORTH E A, KILBERG M S. Asparagine synthetase:regulation by cell stress and involvement in tumor biology[J]. Am J Physiol Endocrinol Metab, 2013, 304(8):E789-E799.
[22] GWINN D M, SWEET-CORDERO A. Abstract B27:Kras alters expression of asparagine synthetase (Asns) in non-small cell lung cancer (NSCLC) and protects tumors during nutrient stress[J]. Mol Cancer Res, 2016, 14(1 Suppl.):B27.
[23] RAVINDRAN R, LOEBBERMANN J, NAKAYA H I, et al. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation[J]. Nature, 2016, 531(7595):523-527.
[24] B'CHIR W, MAURIN A C, CARRARO V, et al. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression[J]. Nucleic Acids Res, 2013, 41(16):7683-7699.
[25] MIZUSHIMA N, KOMATSU M. Autophagy:renovation of cells and tissues[J]. Cell, 2011, 147(4):728-741.
[26] STSSLE S, BRUNTON J, ZIEHR B, et al. Francisella tularensis harvests nutrients derived via ATG5-independent autophagy to support intracellular growth[J]. PLoS Path, 2013, 9(8):e1003562.
[27] BJORDAL M, ARQUIER N, KNIAZEFF J, et al. Sensing of amino acids in a dopaminergic circuitry promotes rejection of an incomplete diet in Drosophila[J]. Cell, 2014, 156(3):510-521.
[28] LAPLANTE M, SABATINI D M. mTOR signaling in growth control and disease[J]. Cell, 2012, 149(2):274-293.
[29] KENNEDY B K, LAMMING D W. The mechanistic target of rapamycin:the grand conductor of metabolism and aging[J]. Cell Metab, 2016, 23(6):990-1003.
[30] HAN J M, JEONG S J, PARK M C, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway[J]. Cell, 2012, 149(2):410-424.
[31] WOLFSON R L, CHANTRANUPONG L, SAXTON R A, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway[J]. Science, 2016, 351(6268):43-48.
[32] HAM D J, CALDOW M K, LYNCH G S, et al. Arginine protects muscle cells from wasting in vitro in an mTORC1-dependent and NO-independent manner[J]. Amino Acids, 2014, 46(12):2643-2652.
[33] CSIBI A, FENDT S M, LI C G, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4[J]. Cell, 2013, 153(4):840-854.
[34] BAR-PELED L, SABATINI D M. Regulation of mTORC1 by amino acids[J]. Trends Cell Biol, 2014, 24(7):400-406.
[35] NICKLIN P, BERGMAN P, ZHANG B L, et al. Bidirectional transport of amino acids regulates mTOR and autophagy[J]. Cell, 2009, 136(3):521-534.
[36] SURYAWAN A, NGUYEN H V, ALMONACI R D, et al. Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated[J]. Amino Acids, 2013, 45(3):523-530.
[37] MOHAN N, SHEN Y, DOKMANOVIC M, et al. VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation[J]. Oncotarget, 2016, 7(32):52239-52254.
[38] DUAN Y H, LI F N, TAN K R, et al. Key mediators of intracellular amino acids signaling to mTORC1 activation[J]. Amino Acids, 2015, 47(5):857-867.
[39] BAR-PELED L, SCHWEITZER L D, ZONCU R, et al. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1[J]. Cell, 2012, 150(6):1196-1208.
[40] JEWELL J L, KIM Y C, RUSSELL R C, et al. Differential regulation of mTORC1 by leucine and glutamine[J]. Science, 2015, 347(6218):194-198.
[41] WAUSON E M, ZAGANJOR E, LEE A Y, et al. The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy[J]. Mol Cell, 2012, 47(6):851-862.
[42] MENON S, DIBBLE C C, TALBOTT G, et al. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome[J]. Cell, 2014, 156(4):771-785.
[43] SUZUKI T, INOKI K. Spatial regulation of the mTORC1 system in amino acids sensing pathway[J]. Acta Bioch Bioph Sin, 2011, 43(9):671-679.
[44] SCHRIEVER S C, DEUTSCH M J, ADAMSKI J, et al. Cellular signaling of amino acids towards mTORC1 activation in impaired human leucine catabolism[J]. J Nutr Biochem, 2013, 24(5):824-831.
[45] ABRAHAM R T. Making sense of amino acid sensing[J]. Science, 2015, 347(6218):128-129.
[46] GOBERDHAN D C I, WILSON C, HARRIS A L. Amino acid sensing by mTORC1:intracellular transporters mark the spot[J]. Cell Metab, 2016, 23(4):580-589.
[47] RUSSELL R C, TIAN Y, YUAN H X, et al. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase[J]. Nat Cell Biol, 2013, 15(7):741-750.
[48] EGAN D, KIM J, SHAW R J, et al. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR[J]. Autophagy, 2011, 7(6):643-644.
[49] KIM J, KUNDU M, VIOLLET B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1[J]. Nat Cell Biol, 2011, 13(2):132-141.

Regulation of GCN2 and mTORC1 Signaling Pathways on Amino Acid Balance in Animal Body

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	LIU Jie, CONG Wei, ZHAO Mindie, ZHAO Ruqian. Expression of GR and FKBP5 in Hippocampus and Hypothalamus of Arbor Acres and Rugao Yellow Broiler Chickens and Its Relationship with Stress Sensitivity [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4766-4776.
[2]	DAI Lingli, LIU Zaixia, GUO Lili, YANG Yanda, CHANG Chencheng, WANG Yu, SHI Caixia, WANG Yuzhen, ZHANG Wenguang. β-Hydroxybutyrate Mediated Epigenetic Modification and Its Molecular Mechanism of Regulating Inflammation [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4095-4104.
[3]	ZHAO Huiying, YU Shiqiang, ZHAO Yuchao, JIANG Linshu. Mechanism of Liver-Adipose Tissue Crosstalk in the Development of Fatty Liver in Periparturient Cows [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4105-4116.
[4]	CAO Xiyue, JI Xiaoxia, ZHANG Chonghao, ZHANG Yafeng, CHEN Yutao, ZHANG Yuanshu. Diminazene Aceturate Alleviates Pulmonary Fibrosis in Mice by Endogenous Activation of ACE2 to Inhibit AngⅡ-TGF-β1 Pathway [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(6): 2631-2640.
[5]	YANG Heng, LI Licai, FU Lin, XU Huihao, ZHANG Dezhi, LI Qianyong. Effect of Prostaglandin D₂ on Endocrine Function and Expression of Apoptosis-related Genes in Goat Luteal Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(4): 1652-1663.
[6]	JIN Meilin, LI Taotao, SUN Dongxiao, WEI Caihong. Research Progress of Epigenetic Regulation in Fat Deposition Mechanism of Livestock and Poultry [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 855-867.
[7]	YE Qianwen, CHEN Zhuo, LI Xin, SUN Yawei, JIN Xiaoye, LI Ziqian, WUMAIERJIANG·Yahefu, ZHONG Qi, MA Xuelian, YAO Gang. Dynamic Changes of Gut Microbiota Composition and Its Predicted Metabolism Function in One-month-old Sucking Lambs [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1095-1108.
[8]	ZHANG Xiyu, ZHAI Pin, WANG Fan, DAI Yingying, ZHAO Bohao, CHEN Yang, WU Xinsheng. Expression and Function of KRT 16 in Hair Follicle Development of Angora Rabbit [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 157-167.
[9]	LIU Zhihao, JIA Peng, LAI Qi, DONG Lifeng, WU Qiujue, GAO Yanhua, TIAN Zhonghong, DIAO Qiyu. Characteristics of Rumen Fermentation and Methane Production in Different Parity Dry Cows [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(12): 4296-4305.
[10]	CAO Xiyue, FU Yali, XIE Nana, ZHANG Yafeng, ZHANG Yuanshu. Inhibitory Effect and Mechanism of Endogenous Activation of Angiotensin Converting Enzyme 2 by Diminazene Aceturate on Cell Lipid Deposition [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(8): 2729-2738.
[11]	GUO Wenliang, XU Yuanqing, JIN Xiao, SHI Binlin. Moderating Role of Heat Shock Protein Under Inflammatory Response and Oxidative Stress Caused by Cold Stress [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(6): 1668-1677.
[12]	YUAN Jing, ZHANG Xinxin, ZHOU Di, YANG Shuai, ZHOU Jiayan, LIANG Aixin, YANG Liguo. Evaluation of the Effect of SS and CST Dual-expression DNA Vaccines with Attenuated Salmonella as Carrier in Immunizing Calves through Different Routes [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(6): 1914-1924.
[13]	SUN Yanjin, XUE Ya’nan, ZHONG Tao, WANG Linjie, LI Li, ZHANG Hongping, ZHAN Siyuan. The Function of HuR and Its Regulation on Muscle Growth and Development [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(5): 1345-1353.
[14]	DING Jun, FU Zilin, HE Junhao, DUAN Xiaowei, MA Lu, BU Dengpan. Research Progress of Milk-derived Exosomes [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(4): 1019-1029.
[15]	LI Yaqi, WANG Xianzhong, ZHANG Jiaojiao. Research Progress of Cell Proliferation and Apoptosis Regulated by Non-thermal Plasma and Its Application in Animal Husbandry [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(1): 1-10.