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PMID: 18701694 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 28 ·No. 33 ·2008-08-13 ·Pages 8316-25

Rodal AA, Motola-Barnes RN, Littleton JT

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.

MeSH Terms
Actins/chemistry,metabolism,physiology Animals Animals, Genetically Modified Cattle Drosophila Drosophila Proteins/genetics,metabolism,physiology Endocytosis/genetics,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
Chemicals
Actins Drosophila Proteins Nerve Tissue Proteins Transforming Growth Factor beta WASp protein, Drosophila Wiskott-Aldrich Syndrome Protein gbb protein, Drosophila nwk protein, Drosophila cdc42 GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rodal Avital A
The Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. [email protected]
Motola-Barnes Rebecca N
Littleton J Troy
References (50)
50 references, click to expand
  1. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins.
    Dev Cell. 2005 Dec;9(6):791-804 PMID: 16326391
  2. BAR, F-BAR (EFC) and ENTH/ANTH domains in the regulation of membrane-cytosol interfaces and membrane curvature.
    Biochim Biophys Acta. 2006 Aug;1761(8):897-912 PMID: 16938488
  3. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal.
    Cell. 2007 Nov 30;131(5):980-93 PMID: 18045539
  4. Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila.
    Neuron. 2006 Mar 16;49(6):833-44 PMID: 16543132
  5. SH3-Hunter: discovery of SH3 domain interaction sites in proteins.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W451-4 PMID: 17485474
  6. Cascade pathway of filopodia formation downstream of SCAR.
    J Cell Sci. 2004 Feb 29;117(Pt 6):837-48 PMID: 14762109
  7. Synaptic development is controlled in the periactive zones of Drosophila synapses.
    Development. 2000 Oct;127(19):4157-68 PMID: 10976048
  8. Harnessing actin dynamics for clathrin-mediated endocytosis.
    Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14 PMID: 16723976
  9. Formin proteins: purification and measurement of effects on actin assembly.
    Methods Enzymol. 2006;406:215-34 PMID: 16472660
  10. Regulation of postsynaptic structure and protein localization by the Rho-type guanine nucleotide exchange factor dPix.
    Neuron. 2001 Nov 8;32(3):415-24 PMID: 11709153
  11. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis.
    Cell. 2007 May 18;129(4):761-72 PMID: 17512409
  12. Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex.
    J Cell Biol. 2000 Sep 18;150(6):1311-20 PMID: 10995437
  13. A protein interaction map of Drosophila melanogaster.
    Science. 2003 Dec 5;302(5651):1727-36 PMID: 14605208
  14. RNAi depleted Drosophila cell extracts to dissect signaling pathways leading to actin polymerization.
    J Biochem Biophys Methods. 2007 Jun 10;70(4):663-9 PMID: 17434595
  15. Altered synaptic development and active zone spacing in endocytosis mutants.
    Curr Biol. 2006 Mar 21;16(6):591-8 PMID: 16546084
  16. The making of filopodia.
    Curr Opin Cell Biol. 2006 Feb;18(1):18-25 PMID: 16337369
  17. Activity-induced rapid synaptic maturation mediated by presynaptic cdc42 signaling.
    Neuron. 2006 May 4;50(3):401-14 PMID: 16675395
  18. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic.
    Nat Cell Biol. 2007 Sep;9(9):1066-73 PMID: 17704769
  19. Complexes of syndapin II with dynamin II promote vesicle formation at the trans-Golgi network.
    J Cell Sci. 2006 Apr 15;119(Pt 8):1504-16 PMID: 16551695
  20. Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.
    Genes Dev. 1994 Aug 1;8(15):1787-802 PMID: 7958857
  21. Dynamin-dependent transferrin receptor recycling by endosome-derived clathrin-coated vesicles.
    Mol Biol Cell. 2002 Jan;13(1):169-82 PMID: 11809831
  22. Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events.
    Development. 2006 Dec;133(23):4655-65 PMID: 17079274
  23. Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.
    Nature. 1999 May 27;399(6734):379-83 PMID: 10360578
  24. Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis.
    J Cell Biol. 2006 Jan 16;172(2):269-79 PMID: 16418535
  25. Protein complexes regulating Arp2/3-mediated actin assembly.
    Curr Opin Cell Biol. 2006 Feb;18(1):4-10 PMID: 16343889
  26. A complexin fusion clamp regulates spontaneous neurotransmitter release and synaptic growth.
    Nat Neurosci. 2007 Oct;10(10):1235-7 PMID: 17873870
  27. Functional analysis of Cdc42 in actin filament assembly, epithelial morphogenesis, and cell signaling during Drosophila development.
    Dev Biol. 2000 May 1;221(1):181-94 PMID: 10772800
  28. Unusual binding properties of the SH3 domain of the yeast actin-binding protein Abp1: structural and functional analysis.
    J Biol Chem. 2002 Feb 15;277(7):5290-8 PMID: 11668184
  29. Synaptic development: insights from Drosophila.
    Curr Opin Neurobiol. 2007 Feb;17(1):35-42 PMID: 17229568
  30. Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11.
    J Cell Biol. 2000 May 15;149(4):901-14 PMID: 10811830
  31. Isolation of mutations in the Drosophila homologues of the human Neurofibromatosis 2 and yeast CDC42 genes using a simple and efficient reverse-genetic method.
    Genetics. 1997 May;146(1):245-52 PMID: 9136014
  32. Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules.
    Nat Neurosci. 2007 Feb;10(2):177-85 PMID: 17220882
  33. The endocytic machinery in nerve terminals surrounds sites of exocytosis.
    Curr Biol. 1999 Dec 2;9(23):1411-4 PMID: 10607569
  34. Spatially distinct binding of Cdc42 to PAK1 and N-WASP in breast carcinoma cells.
    Mol Cell Biol. 2005 Mar;25(5):1680-95 PMID: 15713627
  35. Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin.
    J Biol Chem. 1998 Jul 24;273(30):19108-19 PMID: 9668096
  36. A modified minimal hemolymph-like solution, HL3.1, for physiological recordings at the neuromuscular junctions of normal and mutant Drosophila larvae.
    J Neurogenet. 2004 Apr-Jun;18(2):377-402 PMID: 15763995
  37. Wasp, the Drosophila Wiskott-Aldrich syndrome gene homologue, is required for cell fate decisions mediated by Notch signaling.
    J Cell Biol. 2001 Jan 8;152(1):1-13 PMID: 11149916
  38. Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila.
    Neuron. 2004 Feb 19;41(4):521-34 PMID: 14980202
  39. Retrograde signaling that regulates synaptic development and function at the Drosophila neuromuscular junction.
    Int Rev Neurobiol. 2006;75:267-85 PMID: 17137932
  40. Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis.
    Neuron. 2004 Jul 22;43(2):193-205 PMID: 15260956
  41. Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth.
    Neuron. 2004 Jul 22;43(2):207-19 PMID: 15260957
  42. Endocytosis and the cytoskeleton.
    Int Rev Cytol. 2002;220:93-144 PMID: 12224553
  43. Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2.
    Biochemistry. 2007 Mar 20;46(11):3494-502 PMID: 17302440
  44. Nervous wreck interacts with thickveins and the endocytic machinery to attenuate retrograde BMP signaling during synaptic growth.
    Neuron. 2008 May 22;58(4):507-18 PMID: 18498733
  45. Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein.
    J Biol Chem. 2006 May 12;281(19):13743-13750 PMID: 16461356
  46. Mechanism of actin network attachment to moving membranes: barbed end capture by N-WASP WH2 domains.
    Cell. 2007 Mar 9;128(5):901-13 PMID: 17350575
  47. Identified motor terminals in Drosophila larvae show distinct differences in morphology and physiology.
    J Neurobiol. 2000 May;43(2):186-97 PMID: 10770847
  48. Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons.
    Neuron. 2005 Mar 24;45(6):887-901 PMID: 15797550
  49. Syndapin oligomers interconnect the machineries for endocytic vesicle formation and actin polymerization.
    J Biol Chem. 2006 May 12;281(19):13285-13299 PMID: 16540475
  50. Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.
    Cell. 2004 Jul 23;118(2):203-16 PMID: 15260990
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2304-08.2008
Email
[email protected]
Published
2008-08-13
Pages
8316-25
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2546611
Subset
IM
Grants
NINDS NIH HHS · K99 NS060947-01 · United States
NINDS NIH HHS · R01 NS043244 · United States
NINDS NIH HHS · R01 NS043244-05 · United States
NINDS NIH HHS · R00 NS060947 · United States
NINDS NIH HHS · K99 NS060947 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.2304-08.2008 PMC Full Text View journal details
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