Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter.
Transport of thyroid hormone across the cell membrane is required for its action and metabolism. Recently, a T-type amino acid transporter was cloned which transports aromatic amino acids but not iodothyronines. This transporter belongs to the monocarboxylate transporter (MCT) family and is most homologous with MCT8 (SLC16A2). Therefore, we cloned rat MCT8 and tested it for thyroid hormone transport in Xenopus laevis oocytes. Oocytes were injected with rat MCT8 cRNA, and after 3 days immunofluorescence microscopy demonstrated expression of the protein at the plasma membrane. MCT8 cRNA induced an approximately 10-fold increase in uptake of 10 nM 125I-labeled thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine. Because of the rapid uptake of the ligands, transport was only linear with time for <4 min. MCT8 did not transport Leu, Phe, Trp, or Tyr. [125I]T4 transport was strongly inhibited by L-T4, D-T4, L-T3, D-T3, 3,3',5-triiodothyroacetic acid, N-bromoacetyl-T3, and bromosulfophthalein. T3 transport was less affected by these inhibitors. Iodothyronine uptake in uninjected oocytes was reduced by albumin, but the stimulation induced by MCT8 was markedly increased. Saturation analysis provided apparent Km values of 2-5 microM for T4, T3, and rT3. Immunohistochemistry showed high expression in liver, kidney, brain, and heart. In conclusion, we have identified MCT8 as a very active and specific thyroid hormone transporter.
Friesema
Edith C H
EC
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GE, The Netherlands.
Ganguly
Sumita
S
Abdalla
Amal
A
Manning Fox
Jocelyn E
JE
Halestrap
Andrew P
AP
Visser
Theo J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013963:Thyroid Hormones / Q000378:metabolism*; D014018:Tissue Distribution; D014982:Xenopus laevis
D027501:Monocarboxylic Acid Transporters; D011994:Recombinant Proteins; D013963:Thyroid Hormones; C478998:monocarboxylate transporter 8, rat; D004247:DNA