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Originally published In Press as doi:10.1074/jbc.M100561200 on April 4, 2001

J. Biol. Chem., Vol. 276, Issue 24, 21458-21463, June 15, 2001
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Post-transcriptional Regulation of the Sodium/Iodide Symporter by Thyrotropin*

Claudia RiedelDagger §, Orlie Levy, and Nancy CarrascoDagger ||

From the Dagger  Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461

The Na+/I- symporter (NIS) is a key plasma membrane glycoprotein that mediates active I- transport in the thyroid gland (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460), the first step in thyroid hormone biogenesis. Whereas relatively little is known about the mechanisms by which thyrotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS activity, post-transcriptional events have been suggested to play a role (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 3789-3793). Here we show that TSH induces de novo NIS biosynthesis and modulates the long NIS half-life (~5 days). In addition, we demonstrate that TSH is required for NIS targeting to or retention in the plasma membrane. We further show that NIS is a phosphoprotein and that TSH modulates its phosphorylation pattern. These results provide strong evidence of the major role played by post-transcriptional events in the regulation of NIS by TSH. Beyond their inherent interest, it is also of medical significance that these TSH-dependent regulatory mechanisms may be altered in the large proportion of thyroid cancers in which NIS is predominantly expressed in intracellular compartments, instead of being properly targeted to the plasma membrane.

* This work was supported in part by the National Institutes of Health Grant DK-41544 (to N. C.).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.

§ Supported by the United States Army Medical Research and Materiel Command Office Award BC990754.

Supported by the National Institutes of Health Hepatology Research Training Grant DK-07218. Current address: Wyeth-Lederle Vaccines, 401 North Middletown Rd. 180/216-17, Pearl River, NY 10965.

|| To whom correspondence should be addressed: Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461. Tel.: 718-430-3523; Fax: 718-430-8922; E-mail: carrasco@aecom.yu.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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