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

被引:56
作者
Erin, N
Bronson, SK
Billingsley, ML
机构
[1] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA
[2] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA
关键词
apoptosis; calmodulin; phosphatase; ischemia; IP3-R;
D O I
10.1016/S0306-4522(02)00933-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:541 / 555
页数:15
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