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Related Experiment Videos

mTOR folate sensing links folate availability to trophoblast cell function.

Fredrick J Rosario1, Theresa L Powell1,2, Thomas Jansson1

  • 1Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

The Journal of Physiology
|April 5, 2017
PubMed
Summary

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Mechanistic target of rapamycin (mTOR) acts as a folate sensor in human trophoblast cells, linking maternal folate status to fetal growth. This newly discovered pathway involves the proton-coupled folate transporter (PCFT) and impacts placental function.

Area of Science:

  • Cell Biology
  • Nutritional Science
  • Reproductive Biology

Background:

  • Folate is crucial for DNA synthesis and methylation, essential for fetal development.
  • Maternal folate deficiency is linked to fetal growth restriction, but mechanisms remain unclear.
  • Mechanistic target of rapamycin (mTOR) integrates nutrient signals to regulate cell growth and function.

Purpose of the Study:

  • To investigate the role of mTOR as a folate sensor in primary human trophoblast (PHT) cells.
  • To elucidate the molecular mechanisms linking folate availability to trophoblast cell function and fetal growth.
  • To identify the involvement of the proton-coupled folate transporter (PCFT) in folate sensing by mTOR.

Main Methods:

  • Utilized primary human trophoblast (PHT) cells.
Keywords:
fetal growthmaternal-fetal exchangeplacenta

Related Experiment Videos

  • Investigated mTOR signaling pathways (mTORC1 and mTORC2).
  • Assessed the role of the proton-coupled folate transporter (PCFT, SLC46A1) in folate sensing.

    • Main Results:

    • mTOR functions as a folate sensor in PHT cells.
    • Folate deficiency inhibits mTOR signaling and reduces amino acid transporter activity.
    • PCFT is essential for mTOR-mediated folate sensing, independent of its transport function.
    • Maternal folate levels positively correlate with placental mTORC1/mTORC2 activity.

    Conclusions:

    • A novel molecular mechanism links folate availability to trophoblast cell function via PCFT and mTOR signaling.
    • Placental mTOR folate sensing may mediate the link between maternal folate status and fetal growth.
    • These findings offer insights into diseases like fetal growth restriction, malformations, and cancer.