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ER Calcium and ER Chaperones: New Players in Apoptosis?

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Calreticulin

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

By using calcium ions as an intracellular messenger, cells walk a tight rope between life and death. Because critical cellular functions depend on the precise delivery of Ca2+ at the right time and place, calcium ions must navigate at all times between intracellular calcium stores and target proteins located in the cytosol, the mitochondria, or the nucleus. Due to the toxicity of high Ca2+ concentrations, even slight disruption of the elaborate calcium signaling machinery can have devastating consequences on cell functions: too much or too little calcium at the wrong time and place might lead to rapid cell death by necrosis, or to the induction of the cell death program of apoptosis. ER chaperones, and most notably calreticulin, play a key role in the making and decoding of both normal and pathological calcium signals. Calreticulin is the main Ca2+-binding protein residing in the ER, and as such contributes most of the ER Ca2+ buffering capacity. Calreticulin also acts as a chaperone for several ER Ca2+ transport proteins, and thus indirectly modulates Ca2+ fluxes across the ER membrane. Accordingly, over- or underexpression of calreticulin leads to rapid and severe alterations in ER Ca2+ homeostasis. Calreticulin expression levels are controlled by the ER Ca2+ levels, thus enabling cells to mount an appropriate response during long-term perturbations in ER Ca2+ storage. However, calreticulin levels are also increased by a variety of cellular stress conditions, and this upregulation might contribute to the Ca2+ signaling defects leading to apoptosis. In this chapter, we will review the role of calreticulin and of other ER chaperones in the control of Ca2+ -mediated apoptosis.

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Authors
  1. Nicolas Demaurex
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  2. Maud Frieden
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  3. Serge Arnaudeau
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Editors and Affiliations

  1. Peninsula Medical School, Devon, U.K. MRC Immunochemistry Unit Department of Biochemistry, University of Oxford, Oxford, UK

    Paul Eggleton Ph.D.

  2. CIHR Membrane Protein Research Group Department of Biochemistry, University of Alberta Edmonton, Alberta, Canada

    Marek Michalak Ph.D.

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Demaurex, N., Frieden, M., Arnaudeau, S. (2003). ER Calcium and ER Chaperones: New Players in Apoptosis?. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_13

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  • DOI: https://doi.org/10.1007/978-1-4419-9258-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4862-7

  • Online ISBN: 978-1-4419-9258-1

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