Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor
Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor
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DOI：
10.1016/j.cub.2005.07.030
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发表时间：
2005-08-23
期刊：
影响因子：
9.2
通讯作者：
Maller, JL
中科院分区：
文献类型：
--
作者：
Liu, JJ;Maller, JL
背景：脊椎动物卵母细胞在等待受精时被细胞生长抑制因子 (CSF) 阻滞在第二次减数分裂中期。越来越多的证据表明，抑制后期促进复合物/环体（APC/C）是造成这种停滞的原因。非洲爪蟾 polo 样激酶 1 (Plx1) 是中期-后期转变时 APC/C 激活所必需的，并且在卵受精/激活时钙浓度升高，通过钙调蛋白依赖性激酶 II (CaMKII) 发挥作用，足以激活 APC/C 并终止 CSF 停滞。然而，PIxl 途径和 CaMKII 途径之间的联系尚未确定。结果：Plx1 的过度表达会导致在缺乏钙的情况下 CSF 释放，并且鸡蛋提取物中 Plx1 的消耗会阻止钙和 CaMKII 诱导 CSF 释放。 APC/C 抑制剂 XErpl/Emi2 先前被 CaMK 11 磷酸化，使其成为 Plx1 的良好底物，并且两种激酶共同磷酸化可促进其在鸡蛋提取物中的降解。 Plxl 引起 CaMKII 的钙非依赖性激活的能力增强了该途径。结果确定了 CaMKII 和 PIxl 促进卵子激活的靶标，并定义了第一个已知的 CSF 释放途径，其中仅当 CaMKII 和 Plxl 在受精时钙升高后都处于活跃状态时，APC/C 抑制剂才成为 e 辐射的目标。结论：具有完整 polo-box 结构域的 Plx1 对于释放 CSF 停滞是必要的，并且在过表达时是足够的。它在钙诱导的 CSF 释放途径中与 CaMKII 发挥相同水平，通过与 CaMKII 合作调节 APC/C 调节因子（如 XErp1/Emi2），而不是直接激活 APC/C 本身。
Background: Vertebrate oocytes are arrested at second meiotic metaphase by cytostatic factor (CSF) while awaiting fertilization. Accumulating evidence has suggested that inhibition of the anaphase-promoting complex/cyclosome (APC/C) is responsible for this arrest. Xenopus polo-like kinase 1 (Plx1) is required for activation of the APC/C at the metaphase-anaphase transition, and calcium elevation, upon fertilization/activation of eggs, acting through calmodulin-dependent kinase II (CaMKII) is sufficient to activate the APC/C and terminate CSF arrest. However, connections between the PIxl pathway and the CaMKII pathway have not been identified.Results: Overexpression of Plx1 causes CSF release in the absence of calcium, and depletion of Plx1 from egg extracts blocks induction of CSF release by calcium and CaMKII. Prior phosphorylation of the APC/C inhibitor XErpl/Emi2 by CaMK 11 renders it a good substrate for Plx1, and phosphorylation by both kinases together promotes its degradation in egg extracts. The pathway is enhanced by the ability of Plxl to cause calciumindependent activation of CaMKII. The results identify the targets of CaMKII and PIxl that promote egg activation and define the first known pathway of CSF release in which an APC/C inhibitor is targeted for e radation only when both CaMKII and Plxl are active a er calcium elevation at fertilization.Conclusions: Plx1 with an intact polo-box domain is necessary for release of CSF arrest and sufficient when overexpressed. It acts at the same level as CaMKII in the pathway of calcium-induced CSF release by cooperating with CaMKII to regulate APC/C regulator(s), such as XErp1/Emi2, rather than by directly activating the APC/C itself.