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

S. Roos, Y. Kanai, Puttur D Prasad, T. L. Powell, T. Jansson

Research output: Contribution to journalArticle

83 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume296
Issue number1
DOIs
StatePublished - Jan 1 2009

Fingerprint

Amino Acid Transport Systems
Sirolimus
Protein Isoforms
Amino Acid Transport System L
Neutral Amino Acid Transport Systems
RNA Isoforms
Messenger RNA
Taurine
Trophoblasts
Post Translational Protein Processing
Growth
Real-Time Polymerase Chain Reaction
Proteins
Sodium
Cell Membrane

Keywords

  • System A
  • System L
  • Taurine transporter

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Regulation of placental amino acid transporter activity by mammalian target of rapamycin. / Roos, S.; Kanai, Y.; Prasad, Puttur D; Powell, T. L.; Jansson, T.

In: American Journal of Physiology - Cell Physiology, Vol. 296, No. 1, 01.01.2009.

Research output: Contribution to journalArticle

@article{357bc988bd454614a039eab6e530c4d4,
title = "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.",
keywords = "System A, System L, Taurine transporter",
author = "S. Roos and Y. Kanai and Prasad, {Puttur D} and Powell, {T. L.} and T. Jansson",
year = "2009",
month = "1",
day = "1",
doi = "10.1152/ajpcell.00330.2008",
language = "English (US)",
volume = "296",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Regulation of placental amino acid transporter activity by mammalian target of rapamycin

AU - Roos, S.

AU - Kanai, Y.

AU - Prasad, Puttur D

AU - Powell, T. L.

AU - Jansson, T.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - System A

KW - System L

KW - Taurine transporter

UR - http://www.scopus.com/inward/record.url?scp=58349106216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58349106216&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00330.2008

DO - 10.1152/ajpcell.00330.2008

M3 - Article

VL - 296

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -