Thyroid hormone transport by the heterodimeric human system L amino acid transporter

Citation
Ech. Friesema et al., Thyroid hormone transport by the heterodimeric human system L amino acid transporter, ENDOCRINOL, 142(10), 2001, pp. 4339-4348
Citations number
59
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINOLOGY
ISSN journal
00137227 → ACNP
Volume
142
Issue
10
Year of publication
2001
Pages
4339 - 4348
Database
ISI
SICI code
0013-7227(200110)142:10<4339:THTBTH>2.0.ZU;2-1
Abstract
Transport of thyroid hormone across the cell membrane is required for thyro id hormone action and metabolism. We have investigated the possible transpo rt of iodothyronines by the human system L amino acid transporter, a protei n consisting of the human 4F2 heavy chain and the human LAT1 light chain. X enopus oocytes were injected with the cRNAs coding for human 4F2 heavy chai n and/or human LAT1 light chain, and after 2 d were incubated at 25 C with 0.01-10 muM [I-125]T-4, [I-125]T-3, [I-125]rT(3), or [I-125]3,3'-diiodothyr onine or with 10-100 muM [H-3]arginine, [H-3]leucine, [H-3]phenylalanine, [ H-3]tyrosine, or [H-3]tryptophan. Injection of human 4F2 heavy chain cRNA a lone stimulated the uptake of leucine and arginine due to dimerization of h uman 4F2 heavy chain with an endogenous Xenopus light chain, but did not af fect the uptake of other ligands. Injection of human LAT1 light chain cRNA alone did not stimulate the uptake of any ligand. Coinjection of cRNAs for human 4F2 heavy chain and human LAT1 light chain stimulated the uptake of p henylalanine > tyrosine > leucine > tryptophan (100 mum) and of 3,3'-diiodo thyronine > rT(3) similar to T-3 > T-4 (10 nM), which in all cases was Naindependent. Saturation analysis provided apparent Michaelis constant (K-m) values of 7.9 muM for T-4, 0.8 mum for T-3, 12.5 mum for rT(3), 7.9 muM fo r 3,3'-diiodothyronine, 46 muM for leucine, and 19 muM for tryptophan. Upta ke of leucine, tyrosine, and tryptophan (10 muM) was inhibited by the diffe rent iodothyronines (10 muM), in particular T-3. Vice versa, uptake of 0.1 mum T-3 was almost completely blocked by coincubation with 100 mum leucine, tryptophan, tyrosine, or phenylalanine. Our results demonstrate stereospecific Na+-independent transport of iodothy ronines by the human heterodimeric system L amino acid transporter.