Cortactin is implicated in murine zygotic development.
Cortactin is implicated in murine zygotic development.
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Cortactin 与小鼠合子发育有关。
DOI：
10.1016/j.yexcr.2009.11.018
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发表时间：
2010
影响因子：
3.7
通讯作者：
Zhan,Xi
中科院分区：
文献类型：
--
作者：
Yu,Dan;Zhang,Helin;Blanpied,ThomasA;Smith,Elizabeth;Zhan,Xi
Cortactin是一种皮质丰富的蛋白，与Arp2/3复合体介导的肌动蛋白聚合有关。然而，Cortactin的生理作用仍不清楚。我们已经产生了一种小鼠品系，其中小鼠皮质蛋白的等位基因被基因捕获载体破坏。由此产生的杂合子小鼠发育正常并具有生育能力，但来自杂合子动物的胚胎成纤维细胞在PDGF诱导的膜褶皱中显示出部分损伤。即使在两细胞阶段，也没有检测到纯合子后代或早期胚胎。对卵母细胞的分析显示，受精后纯合子的检测逐渐减少。在停滞于减数分裂中期II(MII)的正常卵母细胞中，Cortactin免疫反应在覆盖母体染色体并与富含肌动蛋白的极化皮质重叠的顶层中被检测到。经肌动蛋白聚合抑制物Latrunculin B处理后，极化的皮质蛋白层的形成减少。减数分裂II恢复后，大部分皮质蛋白积累到第二极体。显微注射皮质蛋白抗体或编码Arp2/3复合体结合缺陷的皮质蛋白突变体的RNA，破坏肌动蛋白帽的完整性，并抑制由孤雌生殖触发的第二极体的发射。我们的数据表明，Cortactin在卵母细胞不对称分裂的机制中发挥着重要作用。
Cortactin is a cortex-enriched protein implicated in Arp2/3 complex-mediated actin polymerization. However, the physiological role of cortactin remains unknown. We have generated a mouse strain in which the allele of murine cortactin was disrupted by a gene trapping vector. The resulting heterozygous mice developed normally and were fertile, but embryonic fibroblasts derived from heterozygous animals displayed partial impairment in PDGF-induced membrane ruffling. No homozygous offspring or early embryos even at the two-cell stage were detected. Analysis of oocytes revealed a gradual decrease in the detection of homozygous zygotes after fertilization. In normal oocytes arrested at meiotic metaphase II (MII), cortactin immunoreactivity was detected in an apical layer that overlies the maternal chromosome and overlaps with a polarized cortex enriched with actin. The formation of the polarized cortactin layer was diminished upon treatment with latrunculin B, an actin polymerization inhibitor. After resumption of meiosis II, the majority of cortactin protein was accumulated into the second polar body. Microinjection of MII-arrested eggs with either cortactin antibody or RNA encoding a cortactin mutant deficient in Arp2/3 complex binding disrupted the integrity of the actin cap and inhibited emission of the second polar body triggered by parthenogenesis. Our data suggest that cortactin plays an important role in the mechanics of asymmetric division in oocytes.