Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila.
We describe the isolation and characterization of nwk (nervous wreck), a temperature-sensitive paralytic mutant that causes excessive growth of larval neuromuscular junctions (NMJs), resulting in increased synaptic bouton number and branch formation. Ultrastructurally, mutant boutons have reduced size and fewer active zones, associated with a reduction in synaptic transmission. nwk encodes an FCH and SH3 domain-containing adaptor protein that localizes to the periactive zone of presynaptic terminals and binds to the Drosophila ortholog of Wasp (Wsp), a key regulator of actin polymerization. wsp null mutants display synaptic overgrowth similar to nwk and enhance the nwk morphological phenotype in a dose-dependent manner. Evolutionarily, Nwk belongs to a previously undescribed family of adaptor proteins that includes the human srGAPs, which regulate Rho activity downstream of Robo receptors. We propose that Nwk controls synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals.
Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA.
Ian P
IP
Coyle
Young-Ho
YH
Koh
Wyan-Ching Mimi
WC
Lee
Jessica
J
Slind
Tim
T
Fergestad
J Troy
JT
Littleton
Barry
B
Ganetzky
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019143:Evolution, Molecular; D008840:Microfilament Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000002:abnormalities* / Q000502:physiology / Q000648:ultrastructure; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein; D018909:src Homology Domains / Q000235:genetics
D033942:Adaptor Proteins, Vesicular Transport; D018076:DNA, Complementary; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C483010:nwk protein, Drosophila