Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / genetics
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Actins / metabolism
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Animals
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Animals, Genetically Modified
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Cell Differentiation / genetics
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Central Nervous System / growth & development*
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Central Nervous System / metabolism
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Central Nervous System / ultrastructure
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Drosophila / growth & development*
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Drosophila / metabolism
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Drosophila / ultrastructure
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Drosophila Proteins
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Dynactin Complex
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Female
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Gene Expression Regulation, Developmental / genetics
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Male
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Motor Neurons / metabolism*
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Motor Neurons / ultrastructure
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Mutation / genetics
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Neuromuscular Junction / growth & development*
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Neuromuscular Junction / metabolism
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Neuromuscular Junction / ultrastructure
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Neuronal Plasticity / genetics
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / pathology
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Presynaptic Terminals / ultrastructure
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RNA / genetics
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Transgenes / genetics
Substances
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ACTRT3 protein, human
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Actins
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Cytoskeletal Proteins
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DCTN1 protein, human
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DCTN1-p150 protein, Drosophila
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Drosophila Proteins
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Dynactin Complex
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Microtubule-Associated Proteins
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RNA