Research article summary (published 19 Oct 2009):

F-BAR proteins of the syndapin family shape the plasma membrane and are crucial for neuromorphogenesis.

Full Abstract

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

Author information

Author/s: Dharmalingam, Elavarasi (E); Haeckel, Akvile (A); Pinyol, Roser (R); Schwintzer, Lukas (L); Koch, Dennis (D); Kessels, Michael Manfred (MM); Qualmann, Britta (B);

Affiliation: Institute for Biochemistry I, Friedrich-Schiller-University Jena, D-07743 Jena, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 42) : pp 13315-27

Dates: Created 2009/10/22; Completed 2009/11/06;

PMID: 19846719, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actin-Related Protein 2-3 Complex - metabolism Actins - metabolism Animals Animals, Newborn Carrier Proteins - chemistry; metabolism Cell Line, Transformed Cell Membrane - physiology Cercopithecus aethiops Conserved Sequence Dendrites - physiology Embryo, Mammalian Endocytosis - genetics Endosomes - metabolism Hippocampus - cytology

Hippocampus - cytology Humans Liposomes Microtubule-Associated Proteins - metabolism Mutation - genetics Neurons - cytology Phosphatidylinositol 4,5-Diphosphate - metabolism RNA, Small Interfering - genetics; metabolism Rats Rats, Wistar Subcellular Fractions - metabolism Transfection - methods Wiskott-Aldrich Syndrome Protein, Neuronal - metabolism cdc42 GTP-Binding Protein - metabolism

Associated Chemicals: Actin-Related Protein 2-3 Complex (0) ; Actins (0) ; Carrier Proteins (0) ; Liposomes (0) ; Microtubule-Associated Proteins (0) ; Mtap2 protein, rat (0) ; Pacsin1 protein, rat (0) ; Phosphatidylinositol 4,5-Diphosphate (0) ; RNA, Small Interfering (0) ; Wiskott-Aldrich Syndrome Protein, Neuronal (0) ; cdc42 GTP-Binding Protein (EC 3.6.5.2)

Related articles

These are the highest related articles currently in the database:

• Actin nucleation: putting the brakes on Arp2/3. 18 May 2008
• EFC/F-BAR proteins and the N-WASP-WIP complex induce membrane curvature-dependent actin polymerization. 14 Oct 2008
• Tuba stimulates intracellular N-WASP-dependent actin assembly. 4 Jun 2006
• Mechanism of actin network attachment to moving membranes: barbed end capture by N-WASP WH2 domains. 7 Mar 2007
• Src phosphorylation of cortactin enhances actin assembly. 30 Jun 2007
• WASp identity theft by a bacterial effector. 30 Aug 2008
• The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. 22 Sep 2007
• Regulation of neuronal morphology by Toca-1, an F-BAR/EFC protein that induces plasma membrane invagination. 31 Jul 2006
• The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency. 21 Jul 2008
• Repetitive N-WASP-binding elements of the enterohemorrhagic Escherichia coli effector EspF(U) synergistically activate actin assembly. 29 Oct 2008

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.