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J. Biol. Chem., Vol. 276, Issue 24, 21458-21463, June 15, 2001
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From the The Na+/I
Post-transcriptional Regulation of the
Sodium/Iodide Symporter by Thyrotropin*
§,
Department of Molecular Pharmacology, Albert
Einstein College of Medicine, Bronx, New York 10461
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.
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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