Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder

Hai Yan Wu, Kazuhito Tomizawa, Hideki Matsui

    Research output: Contribution to journalReview articlepeer-review

    73 Citations (Scopus)

    Abstract

    Intracellular calcium is a powerful secondary messenger that affects a number of calcium sensors, including calpain, a Ca2+-dependent cysteine protease, and calcineurin, a Ca2+ /calmodulin-dependent protein phosphatase. Maintenance of low basal levels of intracellular calcium allows for the tightly regulated physiological activation of these proteins, which is crucial to a wide variety of cellular processes, such as fertilization, proliferation, development, learning, and memory. Deregulation of calpain and calcineurin has been implicated in the pathogenesis of several disorders, including hypertension, heart disease, diabetes, cerebral ischemia, and Alzheimer's disease. Recent studies have demonstrated an interplay between calpain and calcineurin, in which calpain can directly regulate calcineurin activity through proteolysis in glutamate-stimulated neurons in culture and in vivo. The calpain-mediated proteolytic cleavage of calcineurin increases phosphatase activity, which promotes caspase-mediated neuronal cell death. Thus, the activation of the calpain-calcineurin pathway could contribute to calcium-dependent disorders, especially those associated with Alzheimer's disease and myocardial hypertrophy. Here, we focus briefly on recent advances in revealing the structural and functional properties of these 2 calcium-activated proteins, as well as on the interplay between the 2, in an effort to understand how calpain-calcineurin signaling may relate to the pathogenesis of calcium-dependent disorders. Copyright

    Original languageEnglish
    Pages (from-to)123-137
    Number of pages15
    JournalActa medica Okayama
    Volume61
    Issue number3
    Publication statusPublished - Jun 2007

    Keywords

    • Calcineurin
    • Calcium
    • Calpain
    • Neurodegeneration
    • Proteolysis

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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