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Association of the thyrotropin receptor with calnexin, calreticulin and BiP. Efects on the maturation of the receptor.

Abstract : 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), calreticulin (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, calreticulin and BiP all interact with TSHR and that the choice made between these two chaperone systems is crucial because each of them has distinct effects on the folding and stability of this receptor at the endoplasmic reticulum level.
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https://hal.archives-ouvertes.fr/hal-02107408
Contributor : Jean-Louis Franc <>
Submitted on : Tuesday, April 23, 2019 - 4:24:47 PM
Last modification on : Wednesday, April 24, 2019 - 1:37:56 AM

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  • HAL Id : hal-02107408, version 1
  • PUBMED : 12383251

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Sandrine Siffroi-Fernandez, Annie Giraud, Jeanne Lanet, Jean-Louis Franc. Association of the thyrotropin receptor with calnexin, calreticulin and BiP. Efects on the maturation of the receptor.. European Journal of Biochemistry, Wiley, 2002, 269 (20), pp.4930-7. ⟨hal-02107408⟩

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