Dynactin Is Necessary for Synapse Stabilization

• Published in: Neuron (Cambridge, Mass.) Vol. 34; no. 5; pp. 729 - 741
• Main Authors: Eaton, Benjamin A, Fetter, Richard D, Davis, Graeme W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2002; Elsevier Limited
• Subjects: Actins - genetics; Actins - metabolism; Animals; Animals, Genetically Modified; Cell culture; Cell Differentiation - genetics; Cell division; Central Nervous System - growth & development; Central Nervous System - metabolism; Central Nervous System - ultrastructure; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Cytoskeleton; Drosophila - growth & development; Drosophila - metabolism; Drosophila - ultrastructure; Drosophila Proteins; Dynactin Complex; Female; Gene Expression Regulation, Developmental - genetics; Insects; Male; Mammals; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Motor Neurons - metabolism; Motor Neurons - ultrastructure; Mutation - genetics; Neuromuscular Junction - growth & development; Neuromuscular Junction - metabolism; Neuromuscular Junction - ultrastructure; Neuronal Plasticity - genetics; Presynaptic Terminals - metabolism; Presynaptic Terminals - pathology; Presynaptic Terminals - ultrastructure; Proteins; Regulation; RNA - genetics; Transgenes - genetics; Yeast
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(02)00721-3

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.