Biochemical Journal

Research article

Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta

James W. A. RITCHIE, Peter M. TAYLOR

Abstract

The feto-placental unit relies on a maternal supply of indispensable amino acids and iodothyronines for early development and normal growth. We examined the role of the System L transporter in placental uptake of these substances, using the human placental choriocarcinoma cell line BeWo as a model experimental system. BeWo cells express both heavy (4F2hc) and light (LAT1, LAT2) chains of the System L holotransporter. Saturable transport of both l-[3H]tryptophan and [125I]tri-iodo-l-thyronine in BeWo cells includes components sensitive to inhibition by the System-L-specific substrate 2-endoamino-bicycloheptane-2-carboxylic acid; kinetic properties of these components indicate that the 4F2hc-LAT1 transporter isoform is likely to predominate for the carriage of both substances at physiologically relevant concentrations. Both 4F2hc and LAT1 proteins are also expressed in human placental membranes and LAT1 at least is localized largely to the syncytiotrophoblast layer of the term human placenta. The 4F2hc-LAT1 transporter might therefore serve a vital role in supplying the developing fetus and the placenta with both thyroid hormones and indispensable amino acids from the maternal circulation.

  • BeWo cells
  • membrane transport
  • System L
  • tri-iodothyronine
  • tryptophan

Footnotes

  • Abbreviations used: 4F2hc (CD98), heavy chain of System L holotransporter; BCH, 2-endoamino-bicycloheptane-2-carboxylic acid; DS, donkey serum; hLAT, human LAT; LAT, l-type amino acid transporter light chain; MeAiB, methylamino-isobutyric acid; OATP, organic-anion-transporting polypeptide; rT3, (‘reverse’) 3,3′,5′-tri-iodothyronine; RT–PCR, reverse-transcriptase-mediated PCR; T3, 3,3′,5-tri-iodo-l-thyronine; T4, l-thyroxine; TH, thyroid hormone.