Abstract
The active accumulation of I- in the thyroid gland is mediated by the Na(+)-I- symporter and driven by the Na+ gradient generated by the Na+/K(+)-ATPase. Thyrotropin (TSH) stimulates thyroidal I- accumulation. Rat thyroid-derived FRTL-5 cells require TSH to accumulate I-. TSH withdrawal for over 7 days results in complete loss of Na(+)-I-symport activity in these cells [Weiss, S. J., Philp, N. J. and Grollman, E. F. (1984) Endocrinology 114, 1090-1098]. Surprisingly, membrane vesicles prepared from FRTL-5 cells maintained in TSH-free medium [TSH(-)cells]accumulate I-, suggesting that the absence of Na(+)-I- symport activity in TSH(-) cells cannot be due solely to a decrease in the biosynthesis of either the symporter or a putative activating factor. This finding indicates that the Na(+)-I- symporter is present, probably in an inactive state, in TSH(-) cells despite their lack of Na(+)-I- symport activity. Na(+)-I- symport activity in thyroid membrane vesicles is enhanced when conditions for vesicle preparation favor proteolysis. Subcellular fractionation studies in both TSH(+) and TSH(-) cells show that Na(+)-I- symport activity is mostly associated with fractions enriched in plasma membrane rather than in intracellular membranes, suggesting that the Na(+)-I- symporter may constitutively reside in the plasma membrane and may be activated by TSH.
Full text
PDF![3789](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf3/43667/2c908adfe90c/pnas01131-0321.png)
![3790](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf3/43667/bdf83113d044/pnas01131-0322.png)
![3791](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf3/43667/ccbd66341a4d/pnas01131-0323.png)
![3792](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf3/43667/f45746b02b18/pnas01131-0324.png)
![3793](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf3/43667/65880d8a2cfa/pnas01131-0325.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bagchi N., Fawcett D. M. Role of sodium ion in active transport of iodide by cultured thyroid cells. Biochim Biophys Acta. 1973 Aug 22;318(2):235–251. doi: 10.1016/0005-2736(73)90117-x. [DOI] [PubMed] [Google Scholar]
- Carrasco N. Iodide transport in the thyroid gland. Biochim Biophys Acta. 1993 Jun 8;1154(1):65–82. doi: 10.1016/0304-4157(93)90017-i. [DOI] [PubMed] [Google Scholar]
- Clancy B. M., Harrison S. A., Buxton J. M., Czech M. P. Protein synthesis inhibitors activate glucose transport without increasing plasma membrane glucose transporters in 3T3-L1 adipocytes. J Biol Chem. 1991 Jun 5;266(16):10122–10130. [PubMed] [Google Scholar]
- DeTomaso A. W., Xie Z. J., Liu G., Mercer R. W. Expression, targeting, and assembly of functional Na,K-ATPase polypeptides in baculovirus-infected insect cells. J Biol Chem. 1993 Jan 15;268(2):1470–1478. [PubMed] [Google Scholar]
- Fong A. D., Handlogten M. E., Kilberg M. S. Substrate-dependent adaptive regulation and trans-inhibition of System A-mediated amino acid transport. Studies using rat hepatoma plasma membrane vesicles. Biochim Biophys Acta. 1990 Mar;1022(3):325–332. doi: 10.1016/0005-2736(90)90281-r. [DOI] [PubMed] [Google Scholar]
- Golstein P., Abramow M., Dumont J. E., Beauwens R. The iodide channel of the thyroid: a plasma membrane vesicle study. Am J Physiol. 1992 Sep;263(3 Pt 1):C590–C597. doi: 10.1152/ajpcell.1992.263.3.C590. [DOI] [PubMed] [Google Scholar]
- Harrison S. A., Clancy B. M., Pessino A., Czech M. P. Activation of cell surface glucose transporters measured by photoaffinity labeling of insulin-sensitive 3T3-L1 adipocytes. J Biol Chem. 1992 Feb 25;267(6):3783–3788. [PubMed] [Google Scholar]
- Hilgemann D. W. Regulation and deregulation of cardiac Na(+)-Ca2+ exchange in giant excised sarcolemmal membrane patches. Nature. 1990 Mar 15;344(6263):242–245. doi: 10.1038/344242a0. [DOI] [PubMed] [Google Scholar]
- James P., Vorherr T., Krebs J., Morelli A., Castello G., McCormick D. J., Penniston J. T., De Flora A., Carafoli E. Modulation of erythrocyte Ca2+-ATPase by selective calpain cleavage of the calmodulin-binding domain. J Biol Chem. 1989 May 15;264(14):8289–8296. [PubMed] [Google Scholar]
- Jones S. M., Crosby J. R., Salamero J., Howell K. E. A cytosolic complex of p62 and rab6 associates with TGN38/41 and is involved in budding of exocytic vesicles from the trans-Golgi network. J Cell Biol. 1993 Aug;122(4):775–788. doi: 10.1083/jcb.122.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KISSANE J. M., ROBINS E. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958 Jul;233(1):184–188. [PubMed] [Google Scholar]
- Kaminsky S. M., Levy O., Garry M. T., Carrasco N. Inhibition of the Na+/I- symporter by harmaline and 3-amino-1-methyl-5H-pyrido(4,3-b)indole acetate in thyroid cells and membrane vesicles. Eur J Biochem. 1991 Aug 15;200(1):203–207. doi: 10.1111/j.1432-1033.1991.tb21068.x. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Marcocci C., Cohen J. L., Grollman E. F. Effect of actinomycin D on iodide transport in FRTL-5 thyroid cells. Endocrinology. 1984 Dec;115(6):2123–2132. doi: 10.1210/endo-115-6-2123. [DOI] [PubMed] [Google Scholar]
- Nilsson M., Björkman U., Ekholm R., Ericson L. E. Iodide transport in primary cultured thyroid follicle cells: evidence of a TSH-regulated channel mediating iodide efflux selectively across the apical domain of the plasma membrane. Eur J Cell Biol. 1990 Aug;52(2):270–281. [PubMed] [Google Scholar]
- Nilsson M., Björkman U., Ekholm R., Ericson L. E. Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane. Acta Endocrinol (Copenh) 1992 Jan;126(1):67–74. doi: 10.1530/acta.0.1260067. [DOI] [PubMed] [Google Scholar]
- O'Neill B., Magnolato D., Semenza G. The electrogenic, Na+-dependent I- transport system in plasma membrane vesicles from thyroid glands. Biochim Biophys Acta. 1987 Jan 26;896(2):263–274. doi: 10.1016/0005-2736(87)90187-8. [DOI] [PubMed] [Google Scholar]
- Rocmans P. A., Penel J. C., Cantraine F. R., Dumont J. E. Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge. Am J Physiol. 1977 Mar;232(3):E343–E352. doi: 10.1152/ajpendo.1977.232.3.E343. [DOI] [PubMed] [Google Scholar]
- Saji M., Kohn L. D. Effect of hydrocortisone on the ability of thyrotropin to increase deoxyribonucleic acid synthesis and iodide uptake in FRTL-5 rat thyroid cells: opposite regulation of adenosine 3',5'-monophosphate signal action. Endocrinology. 1990 Oct;127(4):1867–1876. doi: 10.1210/endo-127-4-1867. [DOI] [PubMed] [Google Scholar]
- Saji M., Kohn L. D. Insulin and insulin-like growth factor-I inhibit thyrotropin-increased iodide transport in serum-depleted FRTL-5 rat thyroid cells: modulation of adenosine 3',5'-monophosphate signal action. Endocrinology. 1991 Feb;128(2):1136–1143. doi: 10.1210/endo-128-2-1136. [DOI] [PubMed] [Google Scholar]
- Shyjan A. W., Levenson R. Antisera specific for the alpha 1, alpha 2, alpha 3, and beta subunits of the Na,K-ATPase: differential expression of alpha and beta subunits in rat tissue membranes. Biochemistry. 1989 May 30;28(11):4531–4535. doi: 10.1021/bi00437a002. [DOI] [PubMed] [Google Scholar]
- Siliprandi L., Vanni P., Kessler M., Semenza G. Na+-dependent, electroneutral L-ascorbate transport across brush border membrane vesicles from guinea pig small intestine. Biochim Biophys Acta. 1979 Mar 23;552(1):129–142. doi: 10.1016/0005-2736(79)90252-9. [DOI] [PubMed] [Google Scholar]
- Simpson I. A., Cushman S. W. Hormonal regulation of mammalian glucose transport. Annu Rev Biochem. 1986;55:1059–1089. doi: 10.1146/annurev.bi.55.070186.005211. [DOI] [PubMed] [Google Scholar]
- Storrie B., Madden E. A. Isolation of subcellular organelles. Methods Enzymol. 1990;182:203–225. doi: 10.1016/0076-6879(90)82018-w. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valente W. A., Vitti P., Kohn L. D., Brandi M. L., Rotella C. M., Toccafondi R., Tramontano D., Aloj S. M., Ambesi-Impiombato F. S. The relationship of growth and adenylate cyclase activity in cultured thyroid cells: separate bioeffects of thyrotropin. Endocrinology. 1983 Jan;112(1):71–79. doi: 10.1210/endo-112-1-71. [DOI] [PubMed] [Google Scholar]
- Vannucci S. J., Nishimura H., Satoh S., Cushman S. W., Holman G. D., Simpson I. A. Cell surface accessibility of GLUT4 glucose transporters in insulin-stimulated rat adipose cells. Modulation by isoprenaline and adenosine. Biochem J. 1992 Nov 15;288(Pt 1):325–330. doi: 10.1042/bj2880325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vidugiriene J., Menon A. K. Early lipid intermediates in glycosyl-phosphatidylinositol anchor assembly are synthesized in the ER and located in the cytoplasmic leaflet of the ER membrane bilayer. J Cell Biol. 1993 Jun;121(5):987–996. doi: 10.1083/jcb.121.5.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vilijn F., Carrasco N. Expression of the thyroid sodium/iodide symporter in Xenopus laevis oocytes. J Biol Chem. 1989 Jul 15;264(20):11901–11903. [PubMed] [Google Scholar]
- WOLFF J. TRANSPORT OF IODIDE AND OTHER ANIONS IN THE THYROID GLAND. Physiol Rev. 1964 Jan;44:45–90. doi: 10.1152/physrev.1964.44.1.45. [DOI] [PubMed] [Google Scholar]
- Weiss S. J., Philp N. J., Ambesi-Impiombato F. S., Grollman E. F. Thyrotropin-stimulated iodide transport mediated by adenosine 3',5'-monophosphate and dependent on protein synthesis. Endocrinology. 1984 Apr;114(4):1099–1107. doi: 10.1210/endo-114-4-1099. [DOI] [PubMed] [Google Scholar]
- Weiss S. J., Philp N. J., Grollman E. F. Iodide transport in a continuous line of cultured cells from rat thyroid. Endocrinology. 1984 Apr;114(4):1090–1098. doi: 10.1210/endo-114-4-1090. [DOI] [PubMed] [Google Scholar]
- Yu Y. H., Sabatini D. D., Kreibich G. Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides. J Cell Biol. 1990 Oct;111(4):1335–1342. doi: 10.1083/jcb.111.4.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]