Study of the transport of thyroid hormone by transporters of the SLC10 family.
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.
Visser
W Edward
WE
Department of Internal Medicine, Erasmus University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Wong
Wing S
WS
van Mullem
Alies A A
AA
Friesema
Edith C H
EC
Geyer
Joachim
J
Visser
Theo J
TJ
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000737:chemistry / Q000378:metabolism*; D000090803:mu-Crystallins
C000716469:CRYM protein, human; C000716471:Crym protein, rat; D003459:Crystallins; D007457:Iodine Radioisotopes; D029363:Organic Anion Transporters, Sodium-Dependent; D020033:Protein Isoforms; D027981:Symporters; D013963:Thyroid Hormones; C071908:sodium-bile acid cotransporter; D019314:Dehydroepiandrosterone Sulfate; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D000090803:mu-Crystallins