ArticleClinical science (London, England : 1979)2020
Down-regulation of placental Cdc42 and Rac1 links mTORC2 inhibition to decreased trophoblast amino acid transport in human intrauterine growth restriction.
Article in Clinical science (London, England : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications.Journal of clinical medicine · 2026Review
- mTOR Signaling Pathway in Antiphospholipid Syndrome: Pathogenesis and Potential Therapeutic Targets.Drug design, development and therapy · 2026Review
- Deciphering mechanisms leading to preterm birth through post-GWAS integration of multi-omics data.iScience · 2025Article
- Normalization of trophoblast mTOR signaling rescues impaired function in primary human trophoblast cells isolated from pregnancies complicated by fetal growth restriction.Cell death discovery · 2025Article
- PiggyBac transposase-mediated inducible trophoblast-specific knockdown of Mtor decreases placental nutrient transport and fetal growth.Clinical science (London, England : 1979) · 2025Article
- Placental Protein Citrullination Signatures Are Modified in Early- and Late-Onset Fetal Growth Restriction.International journal of molecular sciences · 2025Article
- Trophoblast-specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice.Acta physiologica (Oxford, England) · 2025Article
- Lentivirus-Mediated Trophoblast-Specific Deptor Knockdown Increases Transplacental System A and System L Amino Acid Transport and Fetal Growth in Mice.Function (Oxford, England) · 2025Article
- Regulation of placental amino acid transport in health and disease.Acta physiologica (Oxford, England) · 2024Review
- Trophoblast-specific overexpression of the LAT1 increases transplacental transport of essential amino acids and fetal growth in mice.PNAS nexus · 2024Article
- Overexpression of the LAT1 in primary human trophoblast cells increases the uptake of essential amino acids and activates mTOR signaling.Clinical science (London, England : 1979) · 2023Article
- Placental Remote Control of Fetal Metabolism: Trophoblast mTOR Signaling Regulates Liver IGFBP-1 Phosphorylation and IGF-1 Bioavailability.International journal of molecular sciences · 2023Article
- Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction.Journal of clinical biochemistry and nutrition · 2021Article
- Placental Function and the Development of Fetal Overgrowth and Fetal Growth Restriction.Obstetrics and gynecology clinics of North America · 2021Review
- Active and Inactive Cdc42 Differ in Their Insert Region Conformational Dynamics.Biophysical journal · 2021Article
- Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells.FASEB bioAdvances · 2021Article
- GEFT Inhibits Autophagy and Apoptosis in RhabdomyosarcomaFrontiers in oncology · 2021Article
- Inhibition of mechanistic target of rapamycin signaling decreases levels of O-GlcNAc transferase and increases serotonin release in the human placenta.Clinical science (London, England : 1979) · 2020Article
- Placental function in maternal obesity.Clinical science (London, England : 1979) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Intrauterine growth restriction (IUGR) increases the risk for perinatal complications and metabolic and cardiovascular disease later in life. The syncytiotrophoblast (ST) is the transporting epithelium of the human placenta, and decreased expression of amino acid transporter isoforms in the ST plasma membranes is believed to contribute to IUGR. Placental mechanistic target of rapamycin Complex 2 (mTORC2) signaling is inhibited in IUGR and regulates the trafficking of key amino acid transporter (AAT) isoforms to the ST plasma membrane; however, the molecular mechanisms are unknown. Cdc42 and Rac1 are Rho-GTPases that regulate actin-binding proteins, thereby modulating the structure and dynamics of the actin cytoskeleton. We hypothesized that inhibition of mTORC2 decreases AAT expression in the plasma membrane and amino acid uptake in primary human trophoblast (PHT) cells mediated by down-regulation of Cdc42 and Rac1. mTORC2, but not mTORC1, inhibition decreased the Cdc42 and Rac1 expression. Silencing of Cdc42 and Rac1 inhibited the activity of the System L and A transporters and markedly decreased the trafficking of LAT1 (System L isoform) and SNAT2 (System A isoform) to the plasma membrane. mTORC2 inhibition by silencing of rictor failed to decrease AAT following activation of Cdc42/Rac1. Placental Cdc42 and Rac1 protein expression was down-regulated in human IUGR and was positively correlated with placental mTORC2 signaling. In conclusion, mTORC2 regulates AAT trafficking in PHT cells by modulating Cdc42 and Rac1. Placental mTORC2 inhibition in human IUGR may contribute to decreased placental amino acid transfer and reduced fetal growth mediated by down-regulation of Cdc42 and Rac1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.