Sialylation of human thyrotropin receptor improves and prolonges its cell surface expression

Abstract

Glycosylation of the thyrotropin receptor (TSHR) has been shown to be essential for correct protein folding and for cellsurface 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 This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG/Pa 423/12-1) and the Interdisciplinary Center for Clinical Research at the Faculty of Medicine of the University of Leipzig (Projects B20, Z03, and Z16-CHIP2) and Deutsche Krebshilfe (10652). Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.