CPEB4 Is a Cell Survival Protein Retained in the Nucleus upon Ischemia or Endoplasmic Reticulum Calcium Depletion
CPEB4 Is a Cell Survival Protein Retained in the Nucleus upon Ischemia or Endoplasmic Reticulum Calcium Depletion
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DOI：
10.1128/mcb.00716-10
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发表时间：
2010-12-01
影响因子：
5.3
通讯作者：
Richter, Joel D.
中科院分区：
文献类型：
--
作者：
Kan, Ming-Chung;Oruganty-Das, Aparna;Richter, Joel D.
RNA 结合蛋白 CPEB（细胞质多腺苷酸化元件结合）调节生殖细胞和大脑中的细胞质多腺苷酸化和翻译。在神经元中，CPEB 在突触后位点以及细胞体中被检测到。相关的 CPEB3 蛋白也调节神经元中的翻译，尽管可能不是通过聚腺苷酸化；它与 CPEB4 一样存在于树突和细胞体中。在这里，我们证明用离子型谷氨酸受体激动剂治疗神经元会导致 CPEB4 在细胞核中积聚。所有 CPEB 蛋白都是核-细胞质穿梭蛋白，它们保留在细胞核中，响应钙介导的信号传导和 α-钙/钙调蛋白依赖性激酶蛋白 II (CaMKII) 活性。 CPEB2、-3 和 -4 具有 CPEB 中不存在的保守核输出信号。 CPEB4 对于细胞生存是必需的，并且当体内局灶性缺血以及培养的神经元缺氧和葡萄糖时，CPEB4 会变成细胞核。进一步的分析表明，CPEB4 的核积累是通过 ER 中钙的消耗来控制的，特别是通过肌醇-1,4,5-三磷酸 (IP3) 受体，这表明这些细胞器之间在亚细胞区室之间重新分配蛋白质方面存在通讯。
The RNA binding protein CPEB (cytoplasmic polyadenylation element binding) regulates cytoplasmic polyadenylation and translation in germ cells and the brain. In neurons, CPEB is detected at postsynaptic sites, as well as in the cell body. The related CPEB3 protein also regulates translation in neurons, albeit probably not through polyadenylation; it, as well as CPEB4, is present in dendrites and the cell body. Here, we show that treatment of neurons with ionotropic glutamate receptor agonists causes CPEB4 to accumulate in the nucleus. All CPEB proteins are nucleus-cytoplasm shuttling proteins that are retained in the nucleus in response to calcium-mediated signaling and alpha-calcium/calmodulin-dependent kinase protein II (CaMKII) activity. CPEB2, -3, and -4 have conserved nuclear export signals that are not present in CPEB. CPEB4 is necessary for cell survival and becomes nuclear in response to focal ischemia in vivo and when cultured neurons are deprived of oxygen and glucose. Further analysis indicates that nuclear accumulation of CPEB4 is controlled by the depletion of calcium from the ER, specifically, through the inositol-1,4,5-triphosphate (IP3) receptor, indicating a communication between these organelles in redistributing proteins between subcellular compartments.