Dynactin is necessary for synapse stabilization.
We present evidence that synapse retraction occurs during normal synaptic growth at the Drosophila neuromuscular junction (NMJ). An RNAi-based screen to identify the molecular mechanisms that regulate synapse retraction identified Arp-1/centractin, a subunit of the dynactin complex. Arp-1 dsRNA enhances synapse retraction, and this effect is phenocopied by a mutation in P150/Glued, also a dynactin component. The Glued protein is enriched within the presynaptic nerve terminal, and presynaptic expression of a dominant-negative Glued transgene enhances retraction. Retraction is associated with a local disruption of the synaptic microtubule cytoskeleton. Electrophysiological, ultrastructural, and immunohistochemical data support a model in which presynaptic retraction precedes disassembly of the postsynaptic apparatus. Our data suggests that dynactin functions locally within the presynaptic arbor to promote synapse stability.
Eaton
Benjamin A
BA
Department of Biochemistry and Biophysics, San Francisco, California 94143, USA.
Fetter
Richard D
RD
Davis
Graeme W
GW
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000235:genetics; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012313:RNA / Q000235:genetics; D019076:Transgenes / Q000235:genetics
C445674:ACTRT3 protein, human; D000199:Actins; D003598:Cytoskeletal Proteins; C000606360:DCTN1 protein, human; C105393:DCTN1-p150 protein, Drosophila; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D012313:RNA