A post-ingestive amino acid sensor promotes food consumption in Drosophila  

作　　者：Zhe Yang Rui Huang Xin Fu Gaohang Wang Wei Qi Decai Mao Zhaomei Shi Wei L. Shen Liming Wang 

机构地区：[1]Life Sciences Institute, Zhejiang University, Hangzhou 310058 Zhejiang, China [2]lnnovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058 Zhejiang, China [3]Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Chongqing University, Chongqing 400030, China [4]Medical School, Chongqing University 400030, China [5]School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China [6]Institute of Neuroscience, Shanghai institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [7]University of Chinese Academy of Sciences, Beijing 100049, China [8]Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing 100084, China

出　　处：《Cell Research》2018年第10期1013-1025,共13页细胞研究（英文版）

基　　金：We thank all Wang Lab members for helpful discussions and technical assistance. We thank Pierre Leopold, Zhefeng Gong, Paul Taghert, Yi Rao, the Bloomington Drosophila stock center at Indiana University, and the Tsinghua Fly Center for fly stocks and reagents. We thank Zhaobing Gao and Yanfen Li （Shanghai Institute of Materia Medica） for their help with electrophysiological experiments. We thank Dr. Xiaoming Li and the Molecular Imaging Core Facility of School of Life Science and Technology, ShanghaiTech University for microscopic imaging. We thank members of the Neuroscience Pioneer Club for insightful discussions throughout the course of this study, and Yan Li, Xiaoke Chen, Liqun Luo and Dengke Ma for helpful comments on the manuscript. Danping Chen and Ye Wu provided scientific and administrative support in the laboratory. This study was funded by the National Natural Science Foundation of China （31522026 to L.W. and 31771169 to W.S.）, the Thousand Young Talents Plan （LW. and W.S.）, and the Fundamental Research Funds for the Central Universities （2016QN81010 and 2015XZZX004-33 to L.W.）.

摘　　要：Adequate protein intake is crucial for the sUrvival and well：being of animals. How animals assess prospective protein sources and ensure dietary amino acid intake plays a critical role in protein homeostasis. By using a quantitative：feeding assay, we show that three amino acids, L-glutamate （L-Glu）, L-alanine （L-Ala） and L-as partate （L-Asp）, but not their D-enantiomers or the other 17 natural L-amino acids combined, rapidly promote food consumption in the fruit fly Drosophila melanogaster. This feeding-promoting effect of dietary amino acids is independent of mating experience and internal nutritional：status. In vivo and ex vivo calcium imagings show that six brain neurons expressing diuretic hormone 44 （DH44） can be rapidly and directly activated by these amino acids, suggesting that these neurons are an amino acid sensor. Genetic inactivation of DH44＋ neurons abolishes the increase in food consumption induced by dietary amino acids, whereas genetic activation of these neurons is sufficient to promote feeding, suggesting that DH44＋ neurons mediate the effect of dietary amino acids to promote food consumption. Single-cell transcri ptome analysis and immunostaining reveal that a putative amino acid transporter, CG13248, is enriched in DH44＋ neurons. Knocking down CG13248 expression in DH44＋ neurons blocks the increase ＇n food consumption and eliminates calcium responses induced by dietary amino acids. Therefore, these data identify DH44＋ neuron as a key sensor to detect amino acids and to enhance food intake via a putative transporter CG13248. These results shed critical light on the regulation of protein homeostasis at organismal levels by the nervous system.

关 键 词：传感器识别 食物消费 氨基酸 果蝇 蛋白质来源 基因激活 vivo 神经原 

分 类 号：Q517[生物学—生物化学] TN948.12[电子电信—信号与信息处理]