Research article summary (published 11 Aug 2008):

Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth.

Full Abstract

Regulation of synaptic morphology depends on endocytosis of activated growth signal receptors, but the mechanisms regulating this membrane-trafficking event are unclear. Actin polymerization mediated by Wiskott-Aldrich syndrome protein (WASp) and the actin-related protein 2/3 complex generates forces at multiple stages of endocytosis. FCH-BIN amphiphysin RVS (F-BAR)/SH3 domain proteins play key roles in this process by coordinating membrane deformation with WASp-dependent actin polymerization. However, it is not known how other WASp ligands, such as the small GTPase Cdc42, coordinate with F-BAR/SH3 proteins to regulate actin polymerization at membranes. Nervous Wreck (Nwk) is a conserved neuronal F-BAR/SH3 protein that localizes to periactive zones at the Drosophila larval neuromuscular junction (NMJ) and is required for regulation of synaptic growth via bone morphogenic protein signaling. Here, we show that Nwk interacts with the endocytic proteins dynamin and Dap160 and functions together with Cdc42 to promote WASp-mediated actin polymerization in vitro and to regulate synaptic growth in vivo. Cdc42 function is associated with Rab11-dependent recycling endosomes, and we show that Rab11 colocalizes with Nwk at the NMJ. Together, our results suggest that synaptic growth activated by growth factor signaling is controlled at an endosomal compartment via coordinated Nwk and Cdc42-dependent actin assembly.

Author information

Author/s: Rodal, Avital A (AA); Motola-Barnes, Rebecca N (RN); Littleton, J Troy (JT);

Affiliation: The Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. arodal(-atsign-)mit.edu

Grants: K99 NS060947-01 (Agency:NINDS NIH HHS) ; R01 NS043244-05 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; 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: 2008-Aug; vol 28 (issue 33) : pp 8316-25

Dates: Created 2008/08/14; Completed 2008/09/09; Revised 2009/02/16;

PMID: 18701694, status: MEDLINE (last retrieval date: 3/9/2009, IMS Date: )

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

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - chemistry; metabolism; physiology Animals Animals, Genetically Modified Cattle Drosophila Drosophila Proteins - genetics; metabolism; physiology Endocytosis - genetics; physiology Nerve Tissue Proteins - genetics; metabolism; physiology

Nerve Tissue Proteins - genetics; metabolism; physiology Neuromuscular Junction - genetics; metabolism; physiology Presynaptic Terminals - physiology Protein Transport - genetics; physiology Synapses - genetics; metabolism; physiology Transforming Growth Factor beta - physiology Wiskott-Aldrich Syndrome Protein - metabolism; physiology cdc42 GTP-Binding Protein - physiology

Associated Chemicals: Actins (0) ; Drosophila Proteins (0) ; Nerve Tissue Proteins (0) ; Transforming Growth Factor beta (0) ; WASp protein, Drosophila (0) ; Wiskott-Aldrich Syndrome Protein (0) ; gbb protein, Drosophila (0) ; nervous wreck protein, Drosophila (0) ; cdc42 GTP-Binding Protein (EC 3.6.5.2)

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