Document Detail


The emerging role of mTORC1 signaling in placental nutrient-sensing.
MedLine Citation:
PMID:  22687819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nutrient-sensing signaling pathways regulate cell metabolism and growth in response to altered nutrient levels and growth factor signaling. Because trophoblast cell metabolism and associated signaling 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 signaling 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 signaling 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 signaling constitutes a critical link between maternal nutrient availability and fetal growth, thereby influencing the long-term health of the fetus.
Authors:
T Jansson; I L M H Aye; D C I Goberdhan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-06-10
Journal Detail:
Title:  Placenta     Volume:  33 Suppl 2     ISSN:  1532-3102     ISO Abbreviation:  Placenta     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-04-26     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  England    
Other Details:
Languages:  eng     Pagination:  e23-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Center for Pregnancy and Newborn Research, Department of OB/GYN, University of Texas Health Science Center, Mail Code 7836, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. jansson@uthscsa.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems
Amino Acids / metabolism
Animals
Female
Fetal Growth Retardation
Humans
Maternal-Fetal Exchange
Multiprotein Complexes / physiology*
Placenta / physiology*
Pregnancy
Pregnancy Complications
Prenatal Nutritional Physiological Phenomena
Signal Transduction / physiology*
TOR Serine-Threonine Kinases / physiology*
Trophoblasts
Grant Support
ID/Acronym/Agency:
C38302/A12278//Cancer Research UK; HD 068370/HD/NICHD NIH HHS; R01 HD068370/HD/NICHD NIH HHS; R21 HD071306/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Amino Acids; 0/Multiprotein Complexes; 0/mechanistic target of rapamycin complex 1; EC 2.7.1.1/TOR Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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