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

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.

Characteristics of 3,5,3′-triiodothyronine (T3)-uptake system of tadpole red blood cells: effect of endocrine-disrupting chemicals on cellular T3 response

“…The fact that the T 3 -uptake system in tadpole RBCs was sensitive to taurocholate and bromosulfophthalein but was insensitive to choline suggests the possibility that some of Na + -independent organic anion transporters (Abe et al 1998, Fujiwara et al 2001 are involved in the tadpole T 3 -uptake system. The K m values obtained from our studies were within the same range of those values obtained for the System T-linked T 3 -uptake system , Zhou et al 1990, McLeese & Eales 1996b, but one order of magnitude lower than those values obtained for System L (Blondeau et al 1993, Ritchie et al 1999, Ritchie & Taylor 2001) and the organic anion transporters (rat oatp2 and oatp3, human LST-1 and OATP-E; Abe et al 1998, Fujiwara et al 2001. Therefore, the T 3 -uptake system that is responsible for a major part of saturable T 3 uptake into tadpole RBCs may be the System T-linked uptake system and may be a common feature for rat, bullfrog and rainbow trout RBCs.…”

Metabolic Activation-related CD147-CD98 Complex

“…This result still needs further biochemical confirmation. However, if an MCT8-CD147-CD98hc-LAT1 connection does truly occur, it would be highly relevant toward the understanding of how thyroid hormone might be transported by both the CD98hc-LAT1 complex (56,57) and the CD147-MCT8 complex (58,59). Among the six known light chains that associate with CD98hc (18,35), only the neutral amino acid transporter LAT1 appeared in Table I.…”

Role of amino acid transporter LAT2 in the activation of mTORC1 pathway and the pathogenesis of crescentic glomerulonephritis

“…LAT1 27 has been found in many malignant cells; 28,29 however, its clear expression in normal tissues has been only reported in the vascular endothelial cells forming the blood-brain barrier 30,31 and syncytiotrophoblastic cells of the placenta. 32 Expression of LAT2 has been shown in the epithelium of kidney proximal tubules and the digestive tract. [33][34][35][36][37] LAT3 and LAT4 have been localized to the apical plasma membrane of podocytes 38 and the distal tubules and collecting ducts, 39 respectively.…”