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First published on July 13, 2005; DOI: 10.1124/mol.105.012906

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Received for publication March 18, 2005.
Revised July 13, 2005.
Accepted for publication July 13, 2005.

Sialylation of Human Thyrotropin Receptor Improves and Prolonges Its Cell Surface Expression

Romy Frenzel 1, Knut Krohn 1, Markus Eszlinger 1, Anke Tonjes 1, Ralf Paschke 1*

1 III. Medical Department, University of Leipzig

* Address correspondence to: E-mail: pasr{at}medizin.uni-leipzig.de

Abstract

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 {beta}-galactoside {alpha}(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 co-expressing 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 50-100%. Moreover, western blot analysis with lectins specific for {alpha}(2,3) and {alpha}(2,6)-linked sialic acids and lectin-binding elisa 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.


Key words: Receptor synthesis/trafficking, N-acetyltransferases, Regulation - post-transcriptional


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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]


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