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J Mol Cell Cardiol. 2012 Jan;52(1):62-73. doi: 10.1016/j.yjmcc.2011.10.018. Epub 2011 Oct 29.

Cardiomyocyte calcineurin signaling in subcellular domains: from the sarcolemma to the nucleus and beyond.

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Medizinische Hochschule Hannover, Klinik für Kardiologie und Angiologie, Rebirth - Cluster of Excellence, Carl-Neuberg-Str.1, 30625 Hannover, Germany.


The serine-threonine phosphatase calcineurin is activated in cardiac myocytes in the diseased heart and induces pathological hypertrophy. Calcineurin activity is mainly triggered by calcium/calmodulin binding but also through calpain mediated cleavage. How controlled calcineurin activation is possible in cardiac myocytes, which typically show a 10-fold difference in cytosolic calcium concentration with every heartbeat, has remained enigmatic. It is now emerging that calcineurin activation and signaling occur in subcellular microdomains, in which it is brought together with target proteins and exceedingly high concentrations of calcium in order to induce downstream signaling. We review current evidence of subcellular calcineurin mainly at the sarcolemma and the nucleus, but also in association with the sarcoplasmic reticulum and mitochondria. We also suggest that knowledge about subcellular signaling could help to develop inhibitors of calcineurin in specific microdomains to avoid side-effects that may arise from complete calcineurin inhibition.

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