Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter*
By E. Friesema, Š. Ganguly, Amal Abdalla, Jocelyn E. Manning Fox, A. Halestrap, T. Visser. Journal of Biological Chemistry, 2003
682 citations recorded by the source corpus.
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 ∼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 μm 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.
Subfields: Biochemistry, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e70644663b284ed073d761abefcc76873274cfa4
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Citations in the corpus
- The monocarboxylate transporter family—Role and regulation (2012, background): “Although widely expressed (27), it appears to play a particularly important role in the brain where it is required for the thyroid hormone uptake that is essential for normal brain development (28).”
- Mechanisms of thyroid hormone action. (2012, neutral): “MCT8 was identified as a specific transporter of thyroid hormone and was reported to be located on the X chromosome (53).”
- The monocarboxylate transporter family—Structure and functional characterization (2012, background): “oocytes revealed that both T4 and T3 were transported with high affinity (Km 5 2–5 lM) whilst aromatic amino acids were not transported (40).”
- A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. (2004, background): “MCT10 (TAT1) transports amino acids, and the rat homologue of human MCT8 was found to be a specific thyroid hormone transporter (Friesema et al. 2003).”
- The SLC16 gene family - structure, role and regulation in health and disease. (2013, background): “When expressed in Xenopus laevis oocytes SLC16A2 (MCT8) was shown to be a high affinity thyroid hormone transporter that facilitates the uptake of the iodothyronines T4, T3, rT3, and 3,3-T2 (Km values 2–5 lM) but not sulphated and sulphamated iodothyronines or aromatic amino acids (Phe, Tyr, and Trp”