title: Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo.
abstract: 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-3beta 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.
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, England, UK.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Buttrick
authors.forename: Luke M A
authors.initials: LM
authors.lastname: Beaumont
authors.forename: Jessica
authors.initials: J
authors.lastname: Leitch
authors.forename: Christopher
authors.initials: C
authors.lastname: Yau
authors.forename: Julian R
authors.initials: JR
authors.lastname: Hughes
authors.forename: James G
authors.initials: JG
authors.lastname: Wakefield
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity / Q000235:genetics; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000378:metabolism* / Q000648:ultrastructure; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C467323:APC2 protein, Drosophila; C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051057:Proto-Oncogene Proteins c-akt; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3