Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins
Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins
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DOI：
10.1074/jbc.m411591200
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发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Hajnóczky, G
中科院分区：
文献类型：
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作者：
LIn, XN;Várnai, P;Hajnóczky, G
许多激动剂触发的细胞质Ca 2+（[Ca 2 +]（c））信号通过1，4，5-三磷酸肌醇（IP 3）信使途径建立。该途径被认为使用IP 3受体（IP 3R）和其他Ca 2+通道之间的Ca 2+依赖性局部相互作用，导致整个细胞从内质网协调Ca 2+释放，并将Ca 2+进入和线粒体Ca 2+摄取与Ca 2+释放偶联。为了评估IP 3在支持[Ca 2 +]（c）波传播、钙池操作的Ca 2+进入和线粒体Ca 2+摄取的局部控制机制中的作用，我们使用了两种IP 3结合蛋白（IP 3BP）：1）磷脂酶C样蛋白的PH结构域，p130（p130 PH）; 2）人型IIP 3R的配体结合结构域（IP 3R 224 -605）。正如所预期的，p130 PH-GFP和GFP-IP 3R 224 -605表现为有效的移动的胞质IP 3缓冲液。在COS-7细胞中，IP 3BPs的表达对钙池操作的Ca 2+内流没有影响。然而，IP 3连接的[Ca 2 +] c信号表现为再生波，IP 3BPs减慢了波的传播。最重要的是，IP 3BPs在很大程度上抑制线粒体[Ca 2 +]信号，并降低[Ca 2 +]（c）和线粒体[Ca 2 +]信号之间的关系，表明线粒体与[Ca 2 +]（c）信号断开。这些数据表明，IP 3升高是重要的，以调节本地之间的相互作用IP 3Rs在传播的[Ca 2 +]（c）波和IP 3依赖的同步化的Ca 2+释放事件是至关重要的钙释放和线粒体Ca 2+摄取之间的耦合。
Cytosolic Ca2+ ([Ca2+](c)) signals triggered by many agonists are established through the inositol 1,4,5-trisphosphate (IP3) messenger pathway. This pathway is believed to use Ca2+-dependent local interactions among IP3 receptors (IP3R) and other Ca2+ channels leading to coordinated Ca2+ release from the endoplasmic reticulum throughout the cell and coupling Ca2+ entry and mitochondrial Ca2+ uptake to Ca2+ release. To evaluate the role of IP3 in the local control mechanisms that support the propagation of [Ca2+](c) waves, storeoperated Ca2+ entry, and mitochondrial Ca2+ uptake, we used two IP3-binding proteins (IP3BP): 1) the PH domain of the phospholipase C-like protein, p130 (p130PH); and 2) the ligand-binding domain of the human type-IIP3R (IP3R224-605). As expected, p130PH-GFP and GFP-IP3R224-605 behave as effective mobile cytosolic IP3 buffers. In COS-7 cells, the expression of IP3BPs had no effect on store-operated Ca2+ entry. However, the IP3-linked [Ca2+] c signal appeared as a regenerative wave and IP3BPs slowed down the wave propagation. Most importantly, IP3BPs largely inhibited the mitochondrial [Ca2+] signal and decreased the relationship between the [Ca2+](c) and mitochondrial [Ca2+] signals, indicating disconnection of the mitochondria from the [Ca2+](c) signal. These data suggest that IP3 elevations are important to regulate the local interactions among IP3Rs during propagation of [Ca2+](c) waves and that the IP3-dependent synchronization of Ca2+ release events is crucial for the coupling between Ca2+ release and mitochondrial Ca2+ uptake.