F-BAR Proteins of the Syndapin Family Shape the Plasma Membrane and Are Crucial for Neuromorphogenesis

• DOI: 10.1523/jneurosci.3973-09.2009
• Publication Date: 2009-10-21T17:38:36Z
• Authors: Elavarasi Dharmal...; Akvile Haeckel; Roser Pinyol; Lukas Schwintzer; Dennis Koch; Michael Manfred K...; Britta Qualmann
• Keywords: Wiskott–Aldrich syndrome protein

Coordinated functions of the actin cytoskeleton and microtubules, which require careful control in time space, are indispensable for drastic alterations neuronal morphology during neuromorphogenesis network formation. Actin filament formation driven by Arp2/3 complex its activator neural Wiskott-Aldrich syndrome protein (N-WASP) is important proper axon development. The underlying molecular mechanisms targeting to specific activation N-WASP at plasma membrane, however, have thus far remained elusive. We show that syndapin I critical hereby uses as a cytoskeletal effector. Upon binding, syndapins release autoinhibition. Syndapins cooperate with Cdc42 phosphatidyl-inositol-(4,5)-bisphosphate. furthermore specifically bind phosphatidylserine-containing membranes via their extended F-BAR domain. Dissecting nucleation direct membrane binding vivo, we demonstrate both physiologically relevant required. Constitutive membrane-targeting experiments vivo indicate cell cortex triggered syndapins. Consistent steering downstream effector cortical nucleation, syndapin-induced arborization dependent. syndapin-N-WASP complexes were revealed loss-of-function studies. Knockdown leads impaired development especially phenocopies aberrant branching observed upon deficiency. In contrast, length involves another N-WASP-binding protein, Abp1. Our data reveal crucial different activators ensure fine activity distinct