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When calcium goes wrong: genetic alterations of a ubiquitous signaling route

Nature Genetics volume 34, pages 135–141 (2003)Cite this article

Abstract

In all eukaryotic cells, the cytosolic concentration of calcium ions ([Ca2+]c) is tightly controlled by complex interactions among transporters, pumps, channels and binding proteins. Finely tuned changes in [Ca2+]c modulate a variety of intracellular functions, and disruption of Ca2+ handling leads to cell death. Here we review the human genetic diseases associated with perturbations in the Ca2+ signaling machinery. Despite the importance of Ca2+ in physiology and pathology, the number of known genetic diseases that can be attributed to defects in proteins directly involved in Ca2+ homeostasis is limited to few examples, which will be discussed. This paucity in contrast with the wide molecular repertoire may depend on the extreme severity of the phenotype (leading to death in utero) or, conversely, on functional compensation due to redundancy. In the latter case, it stands to reason that other genetic defects in calcium signaling have yet to be identified owing to their subtle phenotype.

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Figure 1: Scheme of an idealized mammalian cell with the localization of the main players of Ca2+ homeostasis.

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Acknowledgements

We thank G. Cortopassi and M. Brini for critically reading the manuscript. The original work by the authors has been supported by grants from Italian Telethon, Italian Association for Cancer Research, the Italian Ministry of University, the National Research Council, the Human Frontier Science Program, The Italian Space Agency and the European Union.

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Authors and Affiliations

  1. Department of Experimental and Diagnostic Medicine and Interdisciplinary Centre for the Study of Inflammation, University of Ferrara, Section of General Pathology, Via Borsari 46, Ferrara, 44100, Italy

    Rosario Rizzuto

  2. Department of Biomedical Sciences, University of Padova and Venetian Institute of Molecular Medicine, Italy

    Tullio Pozzan

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  1. Rosario Rizzuto
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Correspondence to Rosario Rizzuto.

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Rizzuto, R., Pozzan, T. When calcium goes wrong: genetic alterations of a ubiquitous signaling route. Nat Genet 34, 135–141 (2003). https://doi.org/10.1038/ng0603-135

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