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The Journal of Neuroscience, April 20, 2005, 25(16):4189-4197; doi:10.1523/JNEUROSCI.0149-05.2005

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Development/Plasticity/Repair
Requirement of Cul3 for Axonal Arborization and Dendritic Elaboration in Drosophila Mushroom Body Neurons

Sijun Zhu,² Rosanne Perez,¹ Marc Pan,¹ and Tzumin Lee¹

Departments of ¹Cell and Structural Biology and ²Molecular and Integrative Physiology, University of Illinois, Urbana, Illinois 61801

Cul3 belongs to the family of cullin proteins, which function as scaffold proteins of E3 ubiquitin ligase complexes. Here we show cell-autonomous involvement of Cul3 in axonal arborization and dendritic elaboration of Drosophila mushroom body neurons. Cul3 mutant neurons are defective in terminal morphogenesis of neurites. Interestingly, mutant axons often terminate around branching points. In addition, dendritic elaboration is severely affected in Cul3 mutant neurons. However, loss of Cul3 function does not affect extension of the axons that rarely arborize. Function of cullin-type proteins has been shown to require covalent attachment of Nedd8 (neural precursor cell-expressed developmentally downregulated), a ubiquitin-like protein. Consistent with this notion, Cul3 is inactivated by a mutation in its conserved neddylation site, and Nedd8 mutant neurons exhibit similar neuronal morphogenetic defects. Together, Cul3 plays an essential role in both axonal arborization and proper elaboration of dendrites and may require neddylation for its proper function.

Key words: Drosophila; Cul3; Nedd8; neurite; arborization; mushroom body

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Received Jan 12, 2005; revised February 22, 2005; accepted March 11, 2005.

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