Calreticulin is essential for cardiac development

Nasrin Mesaeli, Kimitoshi Nakamura, Elena Zvaritch, Peter Dickie, Ewa Dziak, Karl Heinz Krause, Michal Opas, David H. MacLennan, Marek Michalak

Research output: Contribution to journalArticle

384 Citations (Scopus)

Abstract

Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt(-/-) cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.

Original languageEnglish
Pages (from-to)857-868
Number of pages12
JournalJournal of Cell Biology
Volume144
Issue number5
DOIs
Publication statusPublished - 8 Mar 1999
Externally publishedYes

Fingerprint

Calreticulin
Umbilical Hernia
Homeostasis
Genes
NFATC Transcription Factors
Cell Nucleus Active Transport
Gene Targeting
Calcineurin
Bradykinin
Cardiovascular System
Green Fluorescent Proteins
Reporter Genes
Knockout Mice
Cell Adhesion
Endoplasmic Reticulum
Transgenic Mice
Carrier Proteins
Transcription Factors
Steroids

Keywords

  • Calcineurin
  • Calcium binding protein
  • Cardiac development
  • Endoplasmic reticulum
  • NF-AT
  • Transcription

ASJC Scopus subject areas

  • Cell Biology

Cite this

Mesaeli, N., Nakamura, K., Zvaritch, E., Dickie, P., Dziak, E., Krause, K. H., ... Michalak, M. (1999). Calreticulin is essential for cardiac development. Journal of Cell Biology, 144(5), 857-868. https://doi.org/10.1083/jcb.144.5.857

Calreticulin is essential for cardiac development. / Mesaeli, Nasrin; Nakamura, Kimitoshi; Zvaritch, Elena; Dickie, Peter; Dziak, Ewa; Krause, Karl Heinz; Opas, Michal; MacLennan, David H.; Michalak, Marek.

In: Journal of Cell Biology, Vol. 144, No. 5, 08.03.1999, p. 857-868.

Research output: Contribution to journalArticle

Mesaeli, N, Nakamura, K, Zvaritch, E, Dickie, P, Dziak, E, Krause, KH, Opas, M, MacLennan, DH & Michalak, M 1999, 'Calreticulin is essential for cardiac development', Journal of Cell Biology, vol. 144, no. 5, pp. 857-868. https://doi.org/10.1083/jcb.144.5.857
Mesaeli N, Nakamura K, Zvaritch E, Dickie P, Dziak E, Krause KH et al. Calreticulin is essential for cardiac development. Journal of Cell Biology. 1999 Mar 8;144(5):857-868. https://doi.org/10.1083/jcb.144.5.857
Mesaeli, Nasrin ; Nakamura, Kimitoshi ; Zvaritch, Elena ; Dickie, Peter ; Dziak, Ewa ; Krause, Karl Heinz ; Opas, Michal ; MacLennan, David H. ; Michalak, Marek. / Calreticulin is essential for cardiac development. In: Journal of Cell Biology. 1999 ; Vol. 144, No. 5. pp. 857-868.
@article{86ef848b40554dd6bb465b7f1ca439c1,
title = "Calreticulin is essential for cardiac development",
abstract = "Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt(-/-) cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.",
keywords = "Calcineurin, Calcium binding protein, Cardiac development, Endoplasmic reticulum, NF-AT, Transcription",
author = "Nasrin Mesaeli and Kimitoshi Nakamura and Elena Zvaritch and Peter Dickie and Ewa Dziak and Krause, {Karl Heinz} and Michal Opas and MacLennan, {David H.} and Marek Michalak",
year = "1999",
month = "3",
day = "8",
doi = "10.1083/jcb.144.5.857",
language = "English",
volume = "144",
pages = "857--868",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Calreticulin is essential for cardiac development

AU - Mesaeli, Nasrin

AU - Nakamura, Kimitoshi

AU - Zvaritch, Elena

AU - Dickie, Peter

AU - Dziak, Ewa

AU - Krause, Karl Heinz

AU - Opas, Michal

AU - MacLennan, David H.

AU - Michalak, Marek

PY - 1999/3/8

Y1 - 1999/3/8

N2 - Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt(-/-) cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.

AB - Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt(-/-) cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.

KW - Calcineurin

KW - Calcium binding protein

KW - Cardiac development

KW - Endoplasmic reticulum

KW - NF-AT

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=0033535353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033535353&partnerID=8YFLogxK

U2 - 10.1083/jcb.144.5.857

DO - 10.1083/jcb.144.5.857

M3 - Article

VL - 144

SP - 857

EP - 868

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -