The emerging role of mTORC1 signaling in placental nutrient-sensing.
The emerging role of mTORC1 signaling in placental nutrient-sensing.
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DOI：
10.1016/j.placenta.2012.05.010
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发表时间：
2012-11
期刊：
影响因子：
3.8
通讯作者：
Goberdhan, D. C. I.
中科院分区：
文献类型：
--
作者：
Jansson, T.;Aye, I. L. M. H.;Goberdhan, D. C. I.
关键词：
营养感应信号通路调节细胞新陈代谢和生长，以响应营养水平和生长因子信号的变化。由于滋养层细胞代谢和相关信号影响胎儿营养物质的利用，滋养层营养感受器可能在调节胎儿生长方面具有独特的作用。我们回顾了支持哺乳动物雷帕霉素复合体靶点1(MTORC1)在胎盘营养感知中的作用的数据。胎盘胰岛素/IGF-I信号和胎儿体内氧气、葡萄糖和氨基酸(AAs)水平在妊娠并发症(如宫内生长受限)中发生改变，所有这些因素都是mTORC1的上游调节因子。此外，mTORC1是胎盘AA转运蛋白的正调节因子，提示滋养层细胞mTORC1调节AA跨胎盘的转运。此外，已知胎盘mTORC1信号也在与胎儿生长改变相关的妊娠并发症中受到调节，以及在母体营养供应发生实验改变的动物模型中受到调节。最近，在确定mTORC1感知AA的分子机制方面取得了重大进展，这一过程需要将mTOR穿梭到晚期的内体和溶酶体隔室(LEL)。我们最近发现，质子辅助氨基酸转运体(PAT/SLC36)家族的成员是AA传感系统的关键组成部分，即调节LEL膜上mTORC1的‘营养体’，将AA转运体及其亚细胞调控置于mTORC1驱动的过程的上游和下游。我们提出了一个模型，在该模型中，胎盘mTORC1信号构成了母体营养供应和胎儿生长之间的关键联系，从而影响胎儿的长期健康。
Nutrient-sensing signalling pathways regulate cell metabolism and growth in response to altered nutrient levels and growth factor signalling. Because trophoblast cell metabolism and associated signalling influence fetal nutrient availability, trophoblast nutrient sensors may have a unique role in regulating fetal growth. We review data in support of a role for mammalian target of rapamycin complex 1 (mTORC1) in placental nutrient-sensing. Placental insulin/IGF-I signalling and fetal levels of oxygen, glucose and amino acids (AAs) are altered in pregnancy complications such as intrauterine growth restriction, and all these factors are well-established upstream regulators of mTORC1. Furthermore, mTORC1 is a positive regulator of placental AA transporters, suggesting that trophoblast mTORC1 modulates AA transfer across the placenta. In addition, placental mTORC1 signalling is also known to be modulated in pregnancy complications associated with altered fetal growth and in animal models in which maternal nutrient availability has been altered experimentally. Recently, significant progress has been made in identifying the molecular mechanisms by which mTORC1 senses AAs, a process requiring shuttling of mTOR to late endosomal and lysosomal compartments (LELs). We recently identified members of the proton-assisted amino acid transporter (PAT/SLC36) family as critical components of the AA-sensing system or ‘nutrisome’ that regulates mTORC1 on LEL membranes, placing AA transporters and their subcellular regulation both upstream and downstream of mTORC1-driven processes. We propose a model in which placental mTORC1 signalling constitutes a critical link between maternal nutrient availability and fetal growth, thereby influencing the long-term health of the fetus.
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影响因子：
3.8
作者：
Ferrazzi, E;Bulfamante, G;Pardi, G
通讯作者：
Pardi, G
影响因子：
10.9
作者：
Howell, Jessica J.;Manning, Brendan D.
通讯作者：
Manning, Brendan D.
DOI：
10.1016/0002-9378(89)90670-4
发表时间：
1989-11-01
影响因子：
9.8
作者：
ECONOMIDES, DL;NICOLAIDES, KH;EVANS, MI
通讯作者：
EVANS, MI
影响因子：
8
作者：
Heublein, S.;Kazi, S.;Oegmundsdottir, M. H.;Attwood, E. V.;Kala, S.;Boyd, C. A. R.;Wilson, C.;Goberdhan, D. C. I.
通讯作者：
Goberdhan, D. C. I.
影响因子：
16
作者：
Düvel K;Yecies JL;Menon S;Raman P;Lipovsky AI;Souza AL;Triantafellow E;Ma Q;Gorski R;Cleaver S;Vander Heiden MG;MacKeigan JP;Finan PM;Clish CB;Murphy LO;Manning BD
通讯作者：
Manning BD