title: Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes.
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 alpha, 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-beta-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.
authors.affiliation: Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Munira
authors.initials: M
authors.lastname: Baqui
authors.forename: Diego
authors.initials: D
authors.lastname: Botero
authors.forename: Balazs
authors.initials: B
authors.lastname: Gereben
authors.forename: Cyntia
authors.initials: C
authors.lastname: Curcio
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: Domenico
authors.initials: D
authors.lastname: Salvatore
authors.forename: Kenji
authors.initials: K
authors.lastname: Sorimachi
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
mesh_terms: D002462:Cell Membrane / Q000201:enzymology*; D002966:Clathrin / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism*
chemical_list: D002966:Clathrin; D007453:Iodide Peroxidase; D005978:Glutathione