TAILIEUCHUNG - Báo cáo Y học:Association of the thyrotropin receptor with calnexin, calreticulin and BiP Effects on the maturation of the receptor

The thyrotropin receptor (TSHR) is a member of the G protein-coupled receptor superfamily. It has by now been clearly established that the maturation of the glycopro-teins synthesized in the endoplasmic reticulum involves interactions with molecular chaperones, which promote the folding and assembly of the glycoproteins. In this study, we investigated whether calnexin (CNX), calreti-culin (CRT) and BiP, three of the main molecular chap-erones present in the endoplasmic reticulum, interact with the TSHR and what effects these interactions might have on the folding of the receptor | Eur. J. Biochem. 269 4930-4937 2002 FEBS 2002 doi Association of the thyrotropin receptor with calnexin calreticulin and BiP Effects on the maturation of the receptor Sandrine Siffroi-Fernandez Annie Giraud Jeanne Lanet and Jean-Louis Franc U555 INSERM Faculte de Medecine Universite de la Mediterranee Marseille France The thyrotropin receptor TSHR is a member of the G protein-coupled receptor superfamily. It has by now been clearly established that the maturation of the glycoproteins synthesized in the endoplasmic reticulum involves interactions with molecular chaperones which promote the folding and assembly of the glycoproteins. In this study we investigated whether calnexin CNX calreti-culin CRT and BiP three of the main molecular chaperones present in the endoplasmic reticulum interact with the TSHR and what effects these interactions might have on the folding of the receptor. In the first set of experiments we observed that in a K562 cell line expressing TSHR about 50 of the receptor synthesized was degraded by the proteasome after ubiquitination. In order to determine whether TSHR interact with CNX CRT and BiP coimmunoprecipitation experiments were performed. TSHR was found to be associated with all three molecular chaperones. To study the role of the interactions between CNX and CRT and the TSHR we used castanospermine a glucosidase I and II inhibitor that blocks the interactions between these chaperones and glycoproteins. In K562 cells expressing the TSHR these drugs led to a faster degradation of the receptor which indicates that these interactions contribute to stabilizing the receptor after its synthesis. The overexpression of calnexin and calreticulin in these cells stabilizes the receptor during the first hour after its synthesis whereas the degradation of TSHR increased in a cell line overexpressing BiP and the quantity of TSHR able to acquire complex type oligosaccharides decreased. These results show that calnexin .

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