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首页> 外文期刊>Cell motility and the cytoskeleton >LIS1 association with dynactin is required for nuclear motility and genomic union in the fertilized mammalian oocyte.
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LIS1 association with dynactin is required for nuclear motility and genomic union in the fertilized mammalian oocyte.

机译:LIS1与动态肌动蛋白的关联对于受精的哺乳动物卵母细胞的核运动和基因组联合是必需的。

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摘要

Mutations in the human LIS1 gene cause the devastating brain disorder lissencephaly. LIS1 also regulates microtubule dynamics; it interacts with the molecular motor cytoplasmic dynein and its cofactor dynactin, and is necessary for neuronal migration. Recently, LIS1 has been suggested to mediate pronuclear migration during fertilization. Here we use rhesus monkey and bovine oocytes, as well as pronucleate-stage bovine zygotes, to determine: Lis1 RNA expression using reverse transcription-polymerase chain reaction; LIS1 protein association with dynactin using immunoprecipitation, Western blot analysis, and immunocytochemistry; and LIS1 function in mediating genomic union using antibody transfection. We find that Lis1 RNA expression increases during fertilization, that LIS1 and dynactin subunit p150/(Glued) co-immunoprecipitate and co-localize to pronuclear surfaces, and that anti-LIS1 antibodies transfected into zygotes dramatically inhibit pronuclear migration and apposition. LIS1 is, therefore, essential to mediate genomic union in a process that involves the dynein-dynactin complex. These results shed light on an additional role for LIS1 and raise implications for human reproduction. Cell Motil. Cytoskeleton 56:245-251, 2003.
机译:人类LIS1基因的突变会导致毁灭性的脑性痴呆。 LIS1还调节微管动力学。它与分子运动细胞质动力蛋白及其辅因子动力蛋白相互作用,是神经元迁移所必需的。最近,有人建议LIS1介导受精过程中的前核迁移。在这里,我们使用恒河猴和牛卵母细胞以及原核阶段的牛受精卵来确定:Lis1 RNA表达采用逆转录聚合酶链反应;使用免疫沉淀,Western印迹分析和免疫细胞化学方法将LIS1蛋白与动力蛋白进行关联; LIS1和LIS1在使用抗体转染介导基因组联合中起作用。我们发现,受精过程中Lis1 RNA的表达增加,LIS1和dynactin亚基p150 /(Glued)共免疫沉淀并共定位于原核表面,转染到受精卵的抗LIS1抗体显着抑制原核迁移和并置。因此,LIS1对于介导涉及动力蛋白-动力蛋白复合物的过程中的基因组联合至关重要。这些结果揭示了LIS1的其他作用,并对人类生殖产生了影响。细胞动力。细胞骨架56:245-251,2003。

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