The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Regulation of placental amino acid transporter activity by mammalian target of rapamycin
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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“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]
Citations
Cites
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
Boney, C. M., Verma, A., Tucker, R., & Vohr, B. R. (2005) · Pediatrics · doi:10.1542/peds.2004-1808 · Cited by 2,303
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097
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Birth Weight and Adult Hypertension, Diabetes Mellitus, and Obesity in US Men
Curhan, G. C., Willett, W. C., Rimm, E. B., Spiegelman, D. L., Ascherio, A., & Stampfer, M. J. (1996) · Circulation · doi:10.1161/01.cir.94.12.3246 · Cited by 917
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Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake
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hVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase
Byfield, M. P., Murray, J. T., & Backer, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507201200 · Cited by 539
Pregnancy Outcomes in Women With Gestational Diabetes Compared With the General Obstetric Population
Casey, B. M. (1997) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(97)00542-5 · Cited by 434
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Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717
Developmental origins of metabolic diseases
Hoffman, D. J., Powell, T. L., Barrett, E. S., & Hardy, D. B. (2020) · Physiological Reviews · doi:10.1152/physrev.00002.2020 · Cited by 504
Self-citationMaternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta
Brett, K., Ferraro, Z. M., Yockell‐Lelièvre, J., Gruslin, A., & Adamo, K. B. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150916153 · Cited by 459
Regulation of Nutrient Transport across the Placenta
Lager, S., & Powell, T. L. (2012) · Journal of Pregnancy · doi:10.1155/2012/179827 · Cited by 484
Self-citationPhysiological role of taurine – from organism to organelle
Lambert, I. H., Kristensen, D. M., Holm, J. B., & Mortensen, O. H. (2014) · Acta Physiologica · doi:10.1111/apha.12365 · Cited by 371
Metadata
- 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
- Publisher
- American Physiological Society
- 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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