Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782148016500637696 |
---|---|
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. |
format | Text |
id | pubmed-2196195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nakamurakimitoshi functionalspecializationofcalreticulindomains AT zuppinianna functionalspecializationofcalreticulindomains AT arnaudeauserge functionalspecializationofcalreticulindomains AT lynchjeffery functionalspecializationofcalreticulindomains AT ahsanirfan functionalspecializationofcalreticulindomains AT krauseryoko functionalspecializationofcalreticulindomains AT pappsylvia functionalspecializationofcalreticulindomains AT desmedthumbert functionalspecializationofcalreticulindomains AT parysjanb functionalspecializationofcalreticulindomains AT mulleresterlwerner functionalspecializationofcalreticulindomains AT lewdanielp functionalspecializationofcalreticulindomains AT krausekarlheinz functionalspecializationofcalreticulindomains AT demaurexnicolas functionalspecializationofcalreticulindomains AT opasmichal functionalspecializationofcalreticulindomains AT michalakmarek functionalspecializationofcalreticulindomains |