title: Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: daichi.kamiyama@ucsf.edu.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kamiyama
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McGorty
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Rie
authors.initials: R
authors.lastname: Kamiyama
authors.affiliation: 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.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kim
authors.affiliation: Department of Biology, University of Miami, Coral Gables, FL 33146, USA; Miami Institute of Molecular Imaging and Computation, Coral Gables, FL 33146, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Chiba
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C090145:Cdc42 protein, Drosophila; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D034741:RNA, Small Interfering; C099753:dock protein, Drosophila; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins