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

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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

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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., Opas, M., MacLennan, D. 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