Study of the transport of thyroid hormone by transporters of the SLC10 family
Molecular and Cellular Endocrinology , Volume 315 - Issue 1-2 p. 138- 145
Transport of (sulfated) iodothyronines across the plasma membrane is required for their intracellular metabolism. Rat Na+/taurocholate cotransporting polypeptide (Ntcp; Slc10a1) has been identified as an important transporter protein. We demonstrate that among the 7 members of the solute carrier family SLC10, only human SLC10A1 mediates sodium-dependent transport of the iodothyronine T4 and iodothyronine sulfates T3S and T4S. In contrast to SLC10A2-7, cells co-expressing SLC10A1 and the deiodinase D1 demonstrate a dramatic increase in T3S and T4S metabolism. The SLC10A1 substrates taurocholate, DHEAS and E3S inhibit T3S and T4S transport. Furthermore, co-transfection of SLC10A1 with CRYM, a well-known intracellular iodothyronine-binding protein, results in an enhanced intracellular accumulation of T3S and T4S, indicating that CRYM binds iodothyronine sulfates. The present findings indicate that the liver-specific transporter SLC10A1 transports (sulfated) iodothyronines, thereby increasing their intracellular availability. Therefore, SLC10A1 may fulfill a critical step in providing liver D1 with iodothyronine sulfates for rapid degradation.
|CRYM, Iodothyronine (sulfates), Mu-crystallin, NTCP, SLC10 family, SLC10A1, Taurocholate, Thyroid hormone, Transporter|
|Molecular and Cellular Endocrinology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Visser, W.E, Wong, W.S, van Mol-van Mullem, A.A.A, Friesema, E.C.H, & Geyer, J. (2010). Study of the transport of thyroid hormone by transporters of the SLC10 family. Molecular and Cellular Endocrinology, 315(1-2), 138–145. doi:10.1016/j.mce.2009.08.003