Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Division / physiology
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Cell Polarity / physiology*
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Central Nervous System / cytology
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Central Nervous System / embryology*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Genes, Dominant
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Mice, Knockout
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Mutation
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Organ Specificity / physiology
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Protein Binding / physiology
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Protein Kinase C / genetics
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Protein Kinase C / metabolism*
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Protein Transport / physiology
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Stem Cells / cytology
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Stem Cells / metabolism*
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Cdc42 protein, Drosophila
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Par6 protein, mouse
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baz protein, Drosophila
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PKC-3 protein
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Protein Kinase C
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GTP-Binding Proteins
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cdc42 GTP-Binding Protein