Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell cycle progression
1Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA.
Development (Cambridge, England)
|July 11, 2008
Summary
Dynamin-associated protein 160 (Dap160) regulates atypical protein kinase C (aPKC) activity and localization. This interaction is crucial for neuroblast cell polarity and cell cycle progression in Drosophila.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Atypical protein kinase C (aPKC) is vital for cell polarization and growth control.
- aPKC dysregulation is implicated in human tumor development.
- Mechanisms regulating aPKC activity remain largely uncharacterized.
Purpose of the Study:
- To identify novel regulators of aPKC.
- To elucidate the role of aPKC in neuroblast cell polarity and proliferation.
Main Methods:
- Biochemical assays to identify interacting proteins.
- In vitro kinase assays to measure aPKC activity.
- Immunofluorescence microscopy to determine protein localization.
- Analysis of mutant phenotypes in Drosophila neuroblasts.
Main Results:
- Dap160 directly interacts with aPKC and enhances its kinase activity in vitro.
- Dap160 colocalizes with aPKC at the apical cortex of neuroblasts.
- Loss of Dap160 leads to aPKC delocalization and reduced activity.
- Mutations in dap160 or aPKC result in fewer proliferating neuroblasts and extended cell cycles.
Conclusions:
- Dap160 acts as a positive regulator of aPKC.
- Dap160 is essential for proper aPKC localization and function.
- Dap160-aPKC pathway is critical for neuroblast cell polarity and cell cycle progression.
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