Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC.
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.
Atwood
Scott X
SX
Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, OR 97403, USA.
Chabu
Chiswili
C
Penkert
Rhiannon R
RR
Doe
Chris Q
CQ
Prehoda
Kenneth E
KE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005799:Genes, Dominant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009928:Organ Specificity / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C090145:Cdc42 protein, Drosophila; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C518597:Par6 protein, mouse; C400774:baz protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein