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Competition between calnexin and BiP in the endoplasmic reticulum can lead to the folding or degradation of human thyroperoxidase

Abstract : Previous studies on the fate of human thyroperoxidase (hTPO) molecules have shown that, after being synthesized, these glycoproteins interact with calnexin and calreticulin and that only some of them are able to acquire a partially folded structure. The aim of the present study was to further investigate the potential role of BiP, another major protein chaperon. Co-immunoprecipitation experiments showed the occurrence of interactions between hTPO and BiP. Pulse-chase studies showed that, when hTPO was expressed in a Chinese hamster ovary cell line overexpressing 5 times more BiP than the parent cells, the rate of hTPO recognized by a monoclonal antibody directed against a conformational structure decreased by 50% after 5 h of chase. Overexpression of the BiP-ATPase mutant G37T also led to a decrease in the correct folding rate of hTPO. When this protein was pulsed in the presence of 35S-(Met + Cys) and the reducing agent dithiotreitol and then chased in a culture medium without dithiothreitol, a 2.5-fold decrease in the correct folding rate was observed in cells overexpressing BiP, whereas co-overexpression of calnexin and Erp57 led to an increase in both the unfolded and partially folded form of hTPO after the pulse step. All of these findings show that BiP and calnexin have opposite effects on the folding behavior of hTPO and that the action of specific molecular chaperones may therefore crucially determine the fate of glycoproteins.
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https://hal.archives-ouvertes.fr/hal-00096576
Contributor : Etienne Challet <>
Submitted on : Tuesday, September 19, 2006 - 4:30:14 PM
Last modification on : Thursday, April 23, 2020 - 2:26:33 PM

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  • HAL Id : hal-00096576, version 1

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Valérie Le Fourn, Sandrine Siffroi-Fernandez, Mireille Ferrand, Jean-Louis Franc. Competition between calnexin and BiP in the endoplasmic reticulum can lead to the folding or degradation of human thyroperoxidase. Biochemistry, American Chemical Society, 2006, 45, pp.7380-7388. ⟨hal-00096576⟩

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