Dear Maud,

The following publications cover the answer to your question:

1-Neuroscience. 2003;117(3):541-55.

Calcium-dependent interaction of calcineurin with Bcl-2 in neuronal tissue.

Erin N1, Bronson SK, Billingsley ML.

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Abstract

Calcineurin, a calmodulin-dependent protein phosphatase, regulates transcription and possibly apoptosis. Previous studies demonstrated that in baby hamster kidney-21 cells after co-transfection calcineurin interacts with Bcl-2, thereby altering transcription and apoptosis. Using co-immunoprecipitation and subcellular fractionation techniques, we observed that calcineurin occurred as a complex with Bcl-2 in various regions of rat and mouse brain. The calcineurin-Bcl-2 complex was identified in mitochondrial, nuclear, microsomal and cytosol fractions. In vitro induction of hypoxia and aglycia or N-methyl-D-aspartate treatment markedly altered both extent of complex formation and its subcellular localization. These observations suggest that Bcl-2 either sequesters calcineurin, that calcineurin dephosphorylates Bcl-2, or that Bcl-2 shuttles calcineurin to specific substrates. Calcineurin also co-immunoprecipitated with the inositol-tris-phosphate receptor. This interaction increased after in vitro hypoxia/aglycia. In Bcl-2 (-/-) mice, interactions between calcineurin- and inositol-tris-phosphate receptor occurred less frequently than in wild-type mice under both control and hypoxic conditions. Experiments involving cell-free systems, as well as brain slices treated with thapsigargin or with N-methyl-D-aspartate suggested that calcium and calmodulin activation of calcineurin leads to interactions between calcineurin and Bcl-2. These data indicate that during times of cellular stress and damage, Bcl-2 targets activated calcineurin to specific compartments and substrates.

http://www.ncbi.nlm.nih.gov/pubmed/12617961

2-J Neurosci. Author manuscript; available in PMC 2005 Sep 13.

Published in final edited form as:

J Neurosci. 2001 Jun 1; 21(11): 4066–4073.

PMCID: PMC1201477

NIHMSID: NIHMS3293

Calcineurin Links Ca2+ Dysregulation with Brain Aging

Thomas C. Foster, Keith M. Sharrow, James R. Masse, Christopher M. Norris, and Ashok Kumar

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The publisher's final edited version of this article is available free at J Neurosci

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Abstract

Brain aging is associated with altered Ca2+ regulation. However, many Ca2+ signal transduction mechanisms have not been explored in the aged brain. Here, we report that cytosolic expression and activity of the Ca2+-dependent protein phosphatase calcineurin (CaN) increases in the hippocampus during aging. CaN changes were paralleled by increased activation, but not expression, of CaN-regulated protein phosphatase 1 and a reduction in the phosphorylation state of CaN substrates involved in cell survival (i.e., Bcl-2-associated death protein and cAMP response element-binding protein). The age-related increase in CaN activity was not attributable to the inability of CaN to translocate to the membrane and was reduced by blocking L-type Ca2+channels. Finally, increased CaN activity correlated with memory function as measured with the Morris water escape task. The results suggest that altered regulation of CaN is one of the processes that could link Ca2+dyshomeostasis to age-related changes in neural function and cognition.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1201477/

Hoping this will be helpful,

Rafik