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Dev Cell. 2015 Oct 12;35(1):93-106. doi: 10.1016/j.devcel.2015.09.007.

Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.

Author information

1
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: daichi.kamiyama@ucsf.edu.
2
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Miami Institute of Molecular Imaging and Computation, Coral Gables, FL 33146, USA; Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
4
Department of Biology, University of Miami, Coral Gables, FL 33146, USA; Miami Institute of Molecular Imaging and Computation, Coral Gables, FL 33146, USA.
5
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: bo.huang@ucsf.edu.

Abstract

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.

PMID:
26460947
PMCID:
PMC4626010
DOI:
10.1016/j.devcel.2015.09.007
[Indexed for MEDLINE]
Free PMC Article

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