PMID- 27690010
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 10
DP  - 2016 Sep 29
TI  - Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate 
      mTORC1.
LID - 1636
AB  - The mammalian target of rapamycin (mTOR) is the central regulator of mammalian 
      cell growth, and is essential for the formation of two structurally and 
      functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple 
      cues such as nutrients, energy status, growth factors and hormones to control 
      cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of 
      the key environmental stimuli, amino acids (AAs), especially leucine, glutamine 
      and arginine, play a crucial role in mTORC1 activation, but where and how AAs are 
      sensed and signal to mTORC1 are not fully understood. Classically, AAs activate 
      mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling 
      initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1)-4F2hc 
      has dual transporter-receptor function that can sense extracellular AA 
      availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9) and 
      cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1) also participate in regulating 
      mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, 
      like G protein-coupled receptor (GPCR) T1R1/T1R3, and regulate mTORC1 without 
      being transported into the cells. Furthermore, AA-dependent mTORC1 activation 
      also initiates within Golgi, which is regulated by Golgi-localized AA transporter 
      PAT4. This review provides an overview of the research progress of the AA sensing 
      mechanisms that regulate mTORC1 activity.
FAU - Zheng, Liufeng
AU  - Zheng L
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. 
      zhenglf2013@webmail.hzau.edu.cn.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. 
      pjm@webmail.hzau.edu.cn.
FAU - Zhou, Yuanfei
AU  - Zhou Y
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. 
      zhouyuanfei@mail.hzau.edu.cn.
AD  - The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China. zhouyuanfei@mail.hzau.edu.cn.
FAU - Li, Fengna
AU  - Li F
AD  - Scientific Observing and Experimental Station of Animal Nutrition and Feed 
      Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering 
      Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes 
      in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of 
      Sciences, Changsha 410125, China. lifengna@isa.ac.cn.
FAU - Wei, Hongkui
AU  - Wei H
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. 
      weihongkui@mail.hzau.edu.cn.
AD  - The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China. weihongkui@mail.hzau.edu.cn.
FAU - Peng, Jian
AU  - Peng J
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. 
      pengjian@mail.hzau.edu.cn.
AD  - The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China. pengjian@mail.hzau.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160929
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
PMC - PMC5085669
OTO - NOTNLM
OT  - amino acids
OT  - mTORC1
OT  - membrane receptor
OT  - membrane transceptor
OT  - sensor
COIS- The authors declare no conflict of interest.
EDAT- 2016/10/01 06:00
MHDA- 2016/10/01 06:00
PMCR- 2016/10/01
CRDT- 2016/10/01 06:00
PHST- 2016/07/07 00:00 [received]
PHST- 2016/09/19 00:00 [revised]
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/10/01 06:00 [entrez]
PHST- 2016/10/01 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
PHST- 2016/10/01 00:00 [pmc-release]
AID - ijms17101636 [pii]
AID - ijms-17-01636 [pii]
AID - 10.3390/ijms17101636 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 Sep 29;17(10):1636. doi: 10.3390/ijms17101636.