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Originally published In Press as doi:10.1074/jbc.M210266200 on November 4, 2002
J. Biol. Chem., Vol. 278, Issue 2, 1206-1211, January 10, 2003
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
From the Thyroid Section, Division of Endocrinology, Diabetes and
Hypertension, Department of Medicine, Brigham and Women's Hospital
and Harvard Medical School, Boston, Massachusetts 02115
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 , 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- -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.
*
This work was supported by Grants DK 36256 and DK 44128 from
the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: 77 Avenue Louis
Pasteur, HIM Bldg., Rm. 560, Boston, MA 02115. Tel.: 617-525-5153; Fax:
617-731-4718; E-mail: abianco@partners.org.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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