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Published online February 11, 2008
doi:10.1083/jcb.200705085
The Journal of Cell Biology, Vol. 180, No. 3, 537-548
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Buttrick et al.
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Article

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

Graham J. Buttrick1, Luke M.A. Beaumont2,3, Jessica Leitch3, Christopher Yau3, Julian R. Hughes1, and James G. Wakefield1,3

1 Department of Zoology, University of Oxford, Oxford OX1 3PS, England, UK
2 Department of Engineering, University of Oxford, Oxford OX1 3PJ, England, UK
3 Life Sciences Interface Doctoral Training Centre, University of Oxford, Oxford OX1 3QD, England, UK

Correspondence to J.G. Wakefield: james.wakefield{at}zoo.ox.ac.uk

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.

Abbreviations used in this paper: APC, adenomatous polyposis coli; Arm, Armadillo; GSK-3, glycogen synthase kinase-3; MT, microtubule; NEB, nuclear envelope breakdown; PI3-K, phosphoinositide 3-kinase; Zw3, Zeste-white 3.


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