Cited by 150Pregnancy and preeclampsia studiesAmino Acid Enzymes and MetabolismPI3K/AKT/mTOR signaling in cancer

Regulation of placental amino acid transporter activity by mammalian target of rapamycin

Roos, S., Kanai, Y., Prasad, P. D., Powell, T. L., Jansson, T.·2009·American Journal of Physiology-Cell Physiology

Abstract

The activity of placental amino acid transporters is decreased in intrauterine growth restriction (IUGR), but the underlying regulatory mechanisms have not been established. Inhibition of the mammalian target of rapamycin (mTOR) signaling pathway has been shown to decrease the activity of the system L amino acid transporter in human placental villous fragments, and placental mTOR activity is decreased in IUGR. In the present study, we used cultured primary trophoblast cells to study mTOR regulation of placental amino acid transporters in more detail and to test the hypothesis that mTOR alters amino acid transport activity by changes in transporter expression. Inhibition of mTOR by rapamycin significantly reduced the activity of system A (−17%), system L (−28%), and taurine (−40%) amino acid transporters. mRNA expression of isoforms of the three amino acid transporter systems in response to mTOR inhibition was measured using quantitative real-time PCR. mRNA expression of l-type amino acid transporter 1 (LAT1; a system L isoform) and taurine transporter was reduced by 13% and 50%, respectively; however, mTOR inhibition did not alter the mRNA expression of system A isoforms (sodium-coupled neutral amino acid transporter-1, -2, and -4), LAT2, or 4F2hc. Rapamycin treatment did not significantly affect the protein expression of any of the transporter isoforms. We conclude that mTOR signaling regulates the activity of key placental amino acid transporters and that this effect is not due to a decrease in total protein expression. These data suggest that mTOR regulates placental amino acid transporters by posttranslational modifications or by affecting transporter translocation to the plasma membrane.

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Crossref · 10.1152/ajpcell.00330.2008

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69 of 69 references verified0 citation errors · 0 not checkable

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  • The mTOR pathway regulates the activity of system A, system L and taurine amino acid transporters in the placenta at the post-translational level, either through modifications or by influencing translocation to the apical membrane.

    “In addition, the mTOR pathway regulates the activity of system A, system L and taurine amino acid transporters in the placenta at the post-translational level, either through modifications or by influencing translocation to the apical membrane (469).”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [469]

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Authors
Roos, S., Kanai, Y., Prasad, P. D., Powell, T. L., & Jansson, T.
Affiliations
  • University of Gothenburg (SE)
  • The University of Osaka (JP)
  • University of Cincinnati (US)
Venue
American Journal of Physiology-Cell Physiology
Published
2009-01
Volume
296
Issue
1
Pages
C142-C150
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
OpenAlex
W2131629100
Cited by
150
References
69
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 8 · 2012: 16
FWCI
5.35
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
mTOR signaling, fetal growth restriction, system L amino acid transporter, system A amino acid transporter, taurine transporter, LAT1, rapamycin, trophoblast, post-translational regulation, placenta
MeSH terms
Taurine Transporters, Cell Survival, Cells, Cultured, Female, Humans, Membrane Glycoproteins, Pregnancy, Protein Kinases, Protein Processing, Post-Translational, RNA, Messenger, Time Factors, Trophoblasts, Signal Transduction, Apoptosis, Sirolimus, Protein Transport, Membrane Transport Proteins, Amino Acid Transport Systems, Amino Acid Transport System A, Amino Acid Transport System L, TOR Serine-Threonine Kinases

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