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Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. (Articolo in rivista) (literal)

Anno

2003-01-01T00:00:00+01:00 (literal)

Alternative label

Di Jeso B., Ulianich L., Pacifico F., Leonardi A., Vito P., Consiglio E., Formisano S. , Arvan P. (2003)
Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum.
in Biochemical journal (Lond., 1984)
(literal)

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Di Jeso B., Ulianich L., Pacifico F., Leonardi A., Vito P., Consiglio E., Formisano S. , Arvan P. (literal)

Pagina inizio

449 (literal)

Pagina fine

458 (literal)

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Impact Factor = 4,326; Interdisciplinarietà del prodotto: The Authors belong to different scientific areas, sectors and Istitutions. The paper was in collaboration with International Institutions. (literal)

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370 (literal)

Rivista

Biochemical journal (Rivista)

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10 (literal)

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During its initial folding in the endoplasmic reticulum (ER), newly synthesized thyroglobulin (Tg) is known to interact with calnexin and other ER molecular chaperones, but its interaction with calreticulin has not been examined previously. In the present study, we have investigated the interactions of endogenous Tg with calreticulin and with several other ER chaperones. We find that, in FRTL-5 and PC-Cl3 cells, calnexin and calreticulin interact with newly synthesized Tg in a carbohydrate-dependent manner, with largely overlapping kinetics that are concomitant with the maturation of Tg intrachain disulphide bonds, preceding Tg dimerization and exit from the ER. Interestingly, thapsigargin treatment induces the premature exit of Tg from the calnexin/calreticulin cycle, while stabilizing and prolonging interactions of Tg with BiP (immunoglobulin heavy chain binding protein) and GRP94 (glucose-regulated protein 94), two chaperones whose binding is not carbohydrate-dependent. Our results suggest that calnexin and calreticulin, acting in ternary complexes with a large glycoprotein substrate such as Tg, might be engaged in the folding of distinct domains, and indicate that lumenal Ca2+ strongly influences the folding of exportable glycoproteins, in part by regulating the balance of substrate binding to different molecular chaperone systems within the ER. (literal)

Note

ISI Web of Science (WOS) (literal)
PubMed (literal)
Scopus (literal)

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Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università degli Studi di Lecce, Italy; Centro di Endocrinologia ed Oncologia Sperimentale 'G. Salvatore' del CNR, Napoli, Italy; Dip. Biologia e Patologia Cellulare e Molecolare 'L. Califano', Napoli, Italy; BioGem Consortium, Napoli, Italy; Division of Endocrinology and Dpt. of Developmental & Molecular Biology, Albert Einstein College of Medicine, New Yoork USA (literal)

Titolo

Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. (literal)

Abstract

During its initial folding in the endoplasmic reticulum (ER), newly synthesized thyroglobulin (Tg) is known to interact with calnexin and other ER molecular chaperones, but its interaction with calreticulin has not been examined previously. In the present study, we have investigated the interactions of endogenous Tg with calreticulin and with several other ER chaperones. We find that, in FRTL-5 and PC-Cl3 cells, calnexin and calreticulin interact with newly synthesized Tg in a carbohydrate-dependent manner, with largely overlapping kinetics that are concomitant with the maturation of Tg intrachain disulphide bonds, preceding Tg dimerization and exit from the ER. Calreticulin co-precipitates more newly synthesized Tg than does calnexin; however, using two different experimental approaches, calnexin and calreticulin were found in ternary complexes with Tg, making this the first endogenous protein reported in ternary complexes with calnexin and calreticulin in the ER of live cells. Depletion of Ca2+ from the ER elicited by thapsigargin (a specific inhibitor of ER Ca2+-ATPases) results in retention of Tg in this organelle. Interestingly, thapsigargin treatment induces the premature exit of Tg from the calnexin/calreticulin cycle, while stabilizing and prolonging interactions of Tg with BiP (immunoglobulin heavy chain binding protein) and GRP94 (glucose-regulated protein 94), two chaperones whose binding is not carbohydrate-dependent. Our results suggest that calnexin and calreticulin, acting in ternary complexes with a large glycoprotein substrate such as Tg, might be engaged in the folding of distinct domains, and indicate that lumenal Ca2+ strongly influences the folding of exportable glycoproteins, in part by regulating the balance of substrate binding to different molecular chaperone systems within the ER. (literal)

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