Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes

Munira Baqui, Diego Botero, Balazs Gereben, Cyntia Curcio, John W. Harney, Domenico Salvatore, Kenji Sorimachi, P. Reed Larsen, Antonio C. Bianco

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95 Citations (Scopus)

Abstract

The type 3 iodothyronine selenodeiodinase (D3) is an integral membrane protein that inactivates thyroid hormones. By using immunofluorescence cytochemistry confocal microscopy of live or fixed cells transiently expressing FLAG-tagged human D3 or monkey hepatocarcinoma cells expressing endogenous D3, we identified D3 in the plasma membrane. It co-localizes with Na,K-ATPase α, with the early endosomal marker EEA-1 and clathrin, but not with two endoplasmic reticulum resident proteins. Most of the D3 molecule is extracellular and can be biotinylated with a cell-impermeant probe. There is constant internalization of D3 that is blocked by sucrose or methyl-β-cyclodextrin-containing medium. Exposing cells to a weak base such as primaquine increases the pool of internalized D3, suggesting that D3 is recycled between plasma membrane and early endosomes. Such recycling could account for the much longer half-life of D3 (12 h) than the thyroxine activating members of the selenodeiodinase family, type 1 (D1; 8 h) or type 2 (D2; 2 h) deiodinase. The extracellular location of D3 gives ready access to circulating thyroid hormones, explaining its capacity for rapid inactivation of circulating thyroxine and triiodothyronine in patients with hemangiomas and its blockade of the access of maternal thyroid hormones to the human fetus.

Original languageEnglish
Pages (from-to)1206-1211
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number2
DOIs
Publication statusPublished - Jan 10 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Baqui, M., Botero, D., Gereben, B., Curcio, C., Harney, J. W., Salvatore, D., Sorimachi, K., Larsen, P. R., & Bianco, A. C. (2003). Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes. Journal of Biological Chemistry, 278(2), 1206-1211. https://doi.org/10.1074/jbc.M210266200