Regulation of N-WASP and the Arp2/3 complex by Abp1 controls neuronal morphology.
Polymerization and organization of actin filaments into complex superstructures is indispensable for structure and function of neuronal networks. We here report that knock down of the F-actin-binding protein Abp1, which is important for endocytosis and synaptic organization, results in changes in axon development virtually identical to Arp2/3 complex inhibition, i.e., a selective increase of axon length. Our in vitro and in vivo experiments demonstrate that Abp1 interacts directly with N-WASP, an activator of the Arp2/3 complex, and releases the autoinhibition of N-WASP in cooperation with Cdc42 and thereby promotes N-WASP-triggered Arp2/3 complex-mediated actin polymerization. In line with our mechanistical studies and the colocalization of Abp1, N-WASP and Arp2/3 at sites of actin polymerization in neurons, we reveal an essential role of Abp1 and its cooperativity with Cdc42 in N-WASP-induced rearrangements of the neuronal cytoskeleton. We furthermore show that introduction of N-WASP mutants lacking the ability to bind Abp1 or Cdc42, Arp2/3 complex inhibition, Abp1 knock down, N-WASP knock down and Arp3 knock down, all cause identical neuromorphological phenotypes. Our data thus strongly suggest that these proteins and their complex formation are important for cytoskeletal processes underlying neuronal network formation.
Pinyol
Roser
R
Research Group Membrane Trafficking and Cytoskeleton, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Haeckel
Akvile
A
Ritter
Anett
A
Qualmann
Britta
B
Kessels
Michael Manfred
MM
D051376:Actin-Related Protein 2-3 Complex / Q000502:physiology*; D006631:Amine Oxidase (Copper-Containing) / Q000502:physiology*; D000818:Animals; D001369:Axons; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D034622:RNA Interference; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000502:physiology*
D051376:Actin-Related Protein 2-3 Complex; D017931:DNA Primers; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D006631:Amine Oxidase (Copper-Containing); C065976:AOC1 protein, human