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Functional specialization of calreticulin domains

Calreticulin is a Ca(2+)-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin as a regulator of Ca(2+) homeostasis. In cells without calreticul...

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Autores principales: Nakamura, Kimitoshi, Zuppini, Anna, Arnaudeau, Serge, Lynch, Jeffery, Ahsan, Irfan, Krause, Ryoko, Papp, Sylvia, De Smedt, Humbert, Parys, Jan B., Müller-Esterl, Werner, Lew, Daniel P., Krause, Karl-Heinz, Demaurex, Nicolas, Opas, Michal, Michalak, Marek
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196195/
https://www.ncbi.nlm.nih.gov/pubmed/11524434
http://dx.doi.org/10.1083/jcb.200102073
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author Nakamura, Kimitoshi
Zuppini, Anna
Arnaudeau, Serge
Lynch, Jeffery
Ahsan, Irfan
Krause, Ryoko
Papp, Sylvia
De Smedt, Humbert
Parys, Jan B.
Müller-Esterl, Werner
Lew, Daniel P.
Krause, Karl-Heinz
Demaurex, Nicolas
Opas, Michal
Michalak, Marek
author_facet Nakamura, Kimitoshi
Zuppini, Anna
Arnaudeau, Serge
Lynch, Jeffery
Ahsan, Irfan
Krause, Ryoko
Papp, Sylvia
De Smedt, Humbert
Parys, Jan B.
Müller-Esterl, Werner
Lew, Daniel P.
Krause, Karl-Heinz
Demaurex, Nicolas
Opas, Michal
Michalak, Marek
author_sort Nakamura, Kimitoshi
collection PubMed
description Calreticulin is a Ca(2+)-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin as a regulator of Ca(2+) homeostasis. In cells without calreticulin, the ER has a lower capacity for Ca(2+) storage, although the free ER luminal Ca(2+) concentration is unchanged. Calreticulin-deficient cells show inhibited Ca(2+) release in response to bradykinin, yet they release Ca(2+) upon direct activation with the inositol 1,4,5-trisphosphate (InsP(3)). These cells fail to produce a measurable level of InsP(3) upon stimulation with bradykinin, likely because the binding of bradykinin to its cell surface receptor is impaired. Bradykinin binding and bradykinin-induced Ca(2+) release are both restored by expression of full-length calreticulin and the N + P domain of the protein. Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca(2+) release but restores the ER Ca(2+) storage capacity. Our results indicate that calreticulin may play a role in folding of the bradykinin receptor, which affects its ability to initiate InsP(3)-dependent Ca(2+) release in calreticulin-deficient cells. We concluded that the C domain of calreticulin plays a role in Ca(2+) storage and that the N domain may participate in its chaperone functions.
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spelling pubmed-21961952008-05-01 Functional specialization of calreticulin domains Nakamura, Kimitoshi Zuppini, Anna Arnaudeau, Serge Lynch, Jeffery Ahsan, Irfan Krause, Ryoko Papp, Sylvia De Smedt, Humbert Parys, Jan B. Müller-Esterl, Werner Lew, Daniel P. Krause, Karl-Heinz Demaurex, Nicolas Opas, Michal Michalak, Marek J Cell Biol Article Calreticulin is a Ca(2+)-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin as a regulator of Ca(2+) homeostasis. In cells without calreticulin, the ER has a lower capacity for Ca(2+) storage, although the free ER luminal Ca(2+) concentration is unchanged. Calreticulin-deficient cells show inhibited Ca(2+) release in response to bradykinin, yet they release Ca(2+) upon direct activation with the inositol 1,4,5-trisphosphate (InsP(3)). These cells fail to produce a measurable level of InsP(3) upon stimulation with bradykinin, likely because the binding of bradykinin to its cell surface receptor is impaired. Bradykinin binding and bradykinin-induced Ca(2+) release are both restored by expression of full-length calreticulin and the N + P domain of the protein. Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca(2+) release but restores the ER Ca(2+) storage capacity. Our results indicate that calreticulin may play a role in folding of the bradykinin receptor, which affects its ability to initiate InsP(3)-dependent Ca(2+) release in calreticulin-deficient cells. We concluded that the C domain of calreticulin plays a role in Ca(2+) storage and that the N domain may participate in its chaperone functions. The Rockefeller University Press 2001-09-03 /pmc/articles/PMC2196195/ /pubmed/11524434 http://dx.doi.org/10.1083/jcb.200102073 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Nakamura, Kimitoshi
Zuppini, Anna
Arnaudeau, Serge
Lynch, Jeffery
Ahsan, Irfan
Krause, Ryoko
Papp, Sylvia
De Smedt, Humbert
Parys, Jan B.
Müller-Esterl, Werner
Lew, Daniel P.
Krause, Karl-Heinz
Demaurex, Nicolas
Opas, Michal
Michalak, Marek
Functional specialization of calreticulin domains
title Functional specialization of calreticulin domains
title_full Functional specialization of calreticulin domains
title_fullStr Functional specialization of calreticulin domains
title_full_unstemmed Functional specialization of calreticulin domains
title_short Functional specialization of calreticulin domains
title_sort functional specialization of calreticulin domains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196195/
https://www.ncbi.nlm.nih.gov/pubmed/11524434
http://dx.doi.org/10.1083/jcb.200102073
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