The type 3 iodothyronine selenodeiodinase (D3) is an integral membrane protein that inactivates thyroid hor- mones. By using immunofluorescence cytochemistry confocal microscopy of live or fixed cells transiently expressing FLAG-tagged human D3 or monkey hepato- carcinoma cells expressing endogenous D3, we identi- fied D3 in the plasma membrane. It co-localizes with Na,K-ATPase , with the early endosomal marker EEA-1 and clathrin, but not with two endoplasmic reticulum resident proteins. Most of the D3 molecule is extracellu- lar and can be biotinylated with a cell-impermeant probe. There is constant internalization of D3 that is blocked by sucrose or methyl- -cyclodextrin-containing medium. Exposing cells to a weak base such as prima- quine 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 hor- mones, 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.

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, and Antonio C. Bianco. Endocrinology. November 4, 2002. doi: 10.1074/jbc.M210266200

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