QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.012906v1 68/4/1106    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frenzel, R. Articles by Paschke, R. Search for Related Content PubMed PubMed Citation Articles by Frenzel, R. Articles by Paschke, R.

Sialylation of Human Thyrotropin Receptor Improves and Prolongs Its Cell-Surface Expression

Medical Department, University of Leipzig, Leipzig, Germany (R.F., K.K., M.E., A.T., R.P.); and Interdisciplinary Center for Clinical Research Leipzig, Leipzig, Germany (K.K.)

Glycosylation of the thyrotropin receptor (TSHR) has been shown to be essential for correct protein folding and for cell-surface targeting. In a recent study, we detected increased expression of -galactoside (2,6)-sialyltransferase (SIAT1) in toxic thyroid adenomas where gain-of-function mutations of the TSHR have been invoked as one of the major causes. To investigate the physiological meaning of these findings, we designed experiments to evaluate the consequences of sialylation for the expression of the TSHR. Hence, we investigated the effect of coexpressing the TSHR and different sialyltransferases (SIAT1, SIAT4a, and SIAT8a) for cell-surface expression of the receptor. Coexpression of each of the three SIAT isoforms and the TSHR in COS-7 cells increased TSHR expression on the cell surface in the range of 50 to 100%. Moreover, Western blot analysis with lectins specific for (2,3) and (2,6)-linked sialic acids and lectin-binding enzyme-linked immunosorbent assay support a direct effect on TSHR cell-surface expression mediated by sialic acid transfer to the TSHR. Finally, we treated living COS-7 cells after cotransfection of TSHR and SIAT8a with neuraminidase for 30 min to remove covalently linked sialic acid. Subsequent loss of TSHR cell-surface expression suggests that sialylation prolongs the resting time of the TSHR on the cell surface. Our data demonstrate for the first time that the transfer of sialic acid can improve and prolong cell-surface expression of a transmembrane receptor.

Address correspondence to: Dr. R. Paschke, III Medical Department, University of Leipzig, Ph.-Rosenthal-Str. 27, D-04103 Leipzig, Germany. E-mail: pasr{at}medizin.uni-leipzig.de

This article has been cited by other articles:

				M. Rivas, B. Mellstrom, B. Torres, G. Cali, A. M. Ferrara, D. Terracciano, M. Zannini, G. Morreale de Escobar, and J. R. Naranjo The DREAM Protein Is Associated with Thyroid Enlargement and Nodular Development Mol. Endocrinol., June 1, 2009; 23(6): 862 - 870. [Abstract] [Full Text] [PDF]

				M. Eszlinger, K. Krohn, A. Kukulska, B. Jarzab, and R. Paschke Perspectives and Limitations of Microarray-Based Gene Expression Profiling of Thyroid Tumors Endocr. Rev., May 1, 2007; 28(3): 322 - 338. [Abstract] [Full Text] [PDF]