Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo.

Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo.
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DOI:
10.1083/jcb.200705085
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发表时间:
2008-02-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Wakefield JG
Wakefield JG
中科院分区:
其他
文献类型:
--
作者:
Buttrick GJ;Beaumont LM;Leitch J;Yau C;Hughes JR;Wakefield JG

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有丝分裂纺锤体的正确定位和形态是通过调节微管(MT)和皮质肌动蛋白之间的相互作用来实现的。在这里,我们发现,在果蝇早期胚胎,蛋白激酶Akt的水平降低导致不完整的皮质核周围的中心体迁移,弯曲的有丝分裂纺锤体,并进入胚胎内部的核损失。我们发现Akt在胚胎皮层富集,并且是糖原合成酶激酶-3 β同源物Zeste-white 3激酶(Zw 3)磷酸化以及结肠腺瘤息肉病(APC)相关蛋白APC 2/E-APC和MT + Tip蛋白EB 1皮质定位所必需的。我们还发现,Akt水平降低导致APC 2在后细胞化胚胎有丝分裂中的错误定位和上皮细胞有丝分裂纺锤体的错误取向。总之,我们的研究结果表明,Akt调节一个复杂的Zw 3,Armadillo,APC 2,和EB 1,这个复杂的稳定MT皮质相互作用的作用,促进中心体分离和有丝分裂纺锤体的方向。
Correct positioning and morphology of the mitotic spindle is achieved through regulating the interaction between microtubules (MTs) and cortical actin. Here we find that, in the Drosophila melanogaster early embryo, reduced levels of the protein kinase Akt result in incomplete centrosome migration around cortical nuclei, bent mitotic spindles, and loss of nuclei into the interior of the embryo. We show that Akt is enriched at the embryonic cortex and is required for phosphorylation of the glycogen synthase kinase-3β homologue Zeste-white 3 kinase (Zw3) and for the cortical localizations of the adenomatosis polyposis coli (APC)–related protein APC2/E-APC and the MT + Tip protein EB1. We also show that reduced levels of Akt result in mislocalization of APC2 in postcellularized embryonic mitoses and misorientation of epithelial mitotic spindles. Together, our results suggest that Akt regulates a complex containing Zw3, Armadillo, APC2, and EB1 and that this complex has a role in stabilizing MT–cortex interactions, facilitating both centrosome separation and mitotic spindle orientation.
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