Developmental Cell
Volume 35, Issue 1, 12 October 2015, Pages 93-106
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Article
Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1

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Highlights

  • Dendrites grow where Pak1 membrane accumulation and Cdc42 activation coincide

  • Pak is localized to the membrane by Dscam1 through Dock, independent of Cdc42

  • Interneuron contact involving Dscam1 guides Dscam1 localization in aCC

  • Dscam1 defines the dendrogenesis site by spatially confining Cdc42 signaling

Summary

Precise positioning of dendritic branches is a critical step in the establishment of neuronal circuitry. However, there is limited knowledge on how environmental cues translate into dendrite initiation or branching at a specific position. Here, through a combination of mutation, RNAi, and imaging experiments, we found that a Dscam-Dock-Pak1 hierarchical interaction defines the stereotypical dendrite growth site in the Drosophila aCC motoneuron. This interaction localizes the Cdc42 effector Pak1 to the plasma membrane at the dendrite initiation site before the activation of Cdc42. Ectopic expression of membrane-anchored Pak1 overrides this spatial specification of dendritogenesis, confirming its function in guiding Cdc42 signaling. We further discovered that Dscam1 localization in aCC occurs through an inter-neuronal contact that involves Dscam1 in the partner MP1 neuron. These findings elucidate a mechanism by which Dscam1 controls neuronal morphogenesis through spatial regulation of Cdc42 signaling and, subsequently, cytoskeletal remodeling.

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