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First published online 28 August 2007
doi: 10.1242/jcs.014902
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Research Article |
1 Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, OR 97403, USA
2 Institute of Molecular Biology, Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA
* Author for correspondence (e-mail: prehoda{at}molbio.uoregon.edu)
Accepted 12 July 2007
Cdc42 recruits Par-6–aPKC to establish cell polarity from worms to mammals. Although Cdc42 is reported to have no function in Drosophila neuroblasts, a model for cell polarity and asymmetric cell division, we show that Cdc42 colocalizes with Par-6–aPKC at the apical cortex in a Bazooka-dependent manner, and is required for Par-6–aPKC localization. Loss of Cdc42 disrupts neuroblast polarity: cdc42 mutant neuroblasts have cytoplasmic Par-6–aPKC, and this phenotype is mimicked by neuroblast-specific expression of a dominant-negative Cdc42 protein or a Par-6 protein that lacks Cdc42-binding ability. Conversely, expression of constitutively active Cdc42 leads to ectopic Par-6–aPKC localization and corresponding cell polarity defects. Bazooka remains apically enriched in cdc42 mutants. Robust Cdc42 localization requires Par-6, indicating the presence of feedback in this pathway. In addition to regulating Par-6–aPKC localization, Cdc42 increases aPKC activity by relieving Par-6 inhibition. We conclude that Cdc42 regulates aPKC localization and activity downstream of Bazooka, thereby directing neuroblast cell polarity and asymmetric cell division.
Key words: Asymmetric cell division, Cell polarity, Kinase regulation, Par complex
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