Thyroid hormone transport by 4F2hc-IU12 heterodimers expressed in Xenopus oocytes.
Thyroid hormone (TH) action and metabolism require hormone transport across cell membranes. We have investigated the possibility that TH are substrates of amino acid transport (System L) mediated by heterodimers of 4F2 heavy-chain (hc) and the light-chain (lc) permease IU12. Co-expression of 4F2hc and IU12 cDNAs injected into Xenopus oocytes induces saturable, Na(+) -independent transport of tri-iodothyronine (T(3)), thyroxine (T(4)) (K(m) of 1.8 and 6.3 microM respectively), tryptophan and phenylalanine. Induced TH and tryptophan uptakes are inhibited by excess BCH (synthetic System L substrate). Induced TH uptake is also inhibited by excess reverse tri-iodothyronine (rT(3)), but not by triodothyroacetic acid (TRIAC) (TH analogue lacking anamino acid moiety). T(3) and tryptophan exhibit reciprocal inhibition of their 4F2hc-IU12 induced uptake. Transport pathways produced by 4F2hc-lc permease complexes may therefore be important routes for movement and exchange of TH (as well as amino acids) across vertebrate cell membranes, with a potential role in modulating TH action.
Ritchie
J W
JW
Department of Anatomy, University of Dundee, Dundee, DD1 4HN, Scotland UK.
Peter
G J
GJ
Shi
Y B
YB
Taylor
P M
PM
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D018929:Cell Culture Techniques; D019281:Dimerization; D005260:Female; D027261:Fusion Regulatory Protein-1; D017874:Immediate-Early Proteins / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D014982:Xenopus laevis
D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; C110598:IU12 protein, Xenopus; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I