气候变化领域集成服务门户(CCPortal): Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply

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DOI	10.1073/pnas.2017092118
	Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply
	Shao X.; Cao G.; Chen D.; Liu J.; Yu B.; Liu M.; Li Y.-X.; Cao B.; Sadovsky Y.; Wang Y.-L.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	During pregnancy, the appropriate allocation of nutrients between the mother and the fetus is dominated by maternal–fetal interactions, which is primarily governed by the placenta. The syncytiotrophoblast (STB) lining at the outer surface of the placental villi is directly bathed in maternal blood and controls feto–maternal exchange. The STB is the largest multinucleated cell type in the human body, and is formed through syncytialization of the mononucleated cytotrophoblast. However, the physiological advantage of forming such an extensively multinucleated cellular structure remains poorly understood. Here, we discover that the STB uniquely adapts to nutrient stress by inducing the macropinocytosis machinery through repression of mammalian target of rapamycin (mTOR) signaling. In primary human trophoblasts and in trophoblast cell lines, differentiation toward a syncytium triggers macropinocytosis, which is greatly enhanced during amino acid shortage, induced by inhibiting mTOR signaling. Moreover, inhibiting mTOR in pregnant mice markedly stimulates macropinocytosis in the syncytium. Blocking macropinocytosis worsens the phenotypes of fetal growth restriction caused by mTOR-inhibition. Consistently, placentas derived from fetal growth restriction patients display: 1) Repressed mTOR signaling, 2) increased syncytialization, and 3) enhanced macropinocytosis. Together, our findings suggest that the unique ability of STB to undergo macropinocytosis serves as an essential adaptation to the cellular nutrient status, and support fetal survival and growth under nutrient deprivation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Placental syncytiotrophoblast \| macropinocytosis \| mTOR \| amino acid shortage \| fetal growth
语种	英语
scopus关键词	amino acid; mammalian target of rapamycin; animal cell; animal experiment; animal tissue; Article; cell culture; cell differentiation; controlled study; embryo; female; fetus; fetus growth; human; human cell; human tissue; intrauterine growth retardation; macropinocytosis; male; maternal nutrition; mouse; mTOR signaling; nonhuman; nutrient supply; placenta; pregnancy; priority journal; survival; syncytiotrophoblast; syncytium; trophoblast; trophoblast cell line
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180940
作者单位	State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 101408, China; Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, United States
推荐引用方式 GB/T 7714	Shao X.,Cao G.,Chen D.,et al. Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply[J],2021,118(3).
APA	Shao X..,Cao G..,Chen D..,Liu J..,Yu B..,...&Wang Y.-L..(2021).Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Shao X.,et al."Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).