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Published on: November 10, 2011
A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons.
Albert H Kim1, Sidharth V Puram, Parizad M Bilimoria
1Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|January 27, 2009
Summary
The anaphase-promoting complex (APC) coactivator Cdc20 is vital for neuron dendrite development. Centrosomal Cdc20-APC signaling regulates dendrite morphogenesis in the mammalian brain.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The anaphase-promoting complex (APC) is a ubiquitin ligase crucial for cell cycle progression.
- Cdc20 is a key coactivator of the APC, primarily known for its role in mitosis.
- Nonmitotic functions of the Cdc20-APC complex remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of Cdc20-APC in postmitotic neurons.
- To explore the nonmitotic functions of the Cdc20-APC complex in neuronal development.
Main Methods:
- Knockdown of Cdc20 in cerebellar slices and in postnatal rats.
- Analysis of dendrite arbor formation using microscopy.
- Investigation of Cdc20 localization within neurons, particularly at the centrosome.
- Assessment of the role of histone deacetylase 6 (HDAC6) in Cdc20 function.
Main Results:
- Cdc20 knockdown significantly impairs dendrite arbor formation in cerebellar granule neurons.
- Cdc20 is localized to the centrosome in neurons, and this localization is essential for dendrite development.
- Histone deacetylase 6 (HDAC6) enhances Cdc20 polyubiquitination and stimulates centrosomal Cdc20-APC activity.
- HDAC6 promotes dendrite differentiation through the centrosomal Cdc20-APC pathway.
Conclusions:
- Cdc20-APC has a critical, previously unrecognized role in dendrite morphogenesis in postmitotic neurons.
- Centrosomal localization of Cdc20-APC defines a novel ubiquitin signaling pathway in neuronal development.
- This pathway has significant implications for understanding neuronal connectivity and plasticity.
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