Abstract
In a forward screen for genes affecting neurotransmission in Drosophila, we identified mutations in dynamin-related protein (drp1). DRP1 is required for proper cellular distribution of mitochondria, and in mutant neurons, mitochondria are largely absent from synapses, thus providing a genetic tool to assess the role of mitochondria at synapses. Although resting Ca2+ is elevated at drp1 NMJs, basal synaptic properties are barely affected. However, during intense stimulation, mutants fail to maintain normal neurotransmission. Surprisingly, FM1-43 labeling indicates normal exo- and endocytosis, but a specific inability to mobilize reserve pool vesicles, which is partially rescued by exogenous ATP. Using a variety of drugs, we provide evidence that reserve pool recruitment depends on mitochondrial ATP production downstream of PKA signaling and that mitochondrial ATP limits myosin-propelled mobilization of reserve pool vesicles. Our data suggest a specific role for mitochondria in regulating synaptic strength.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cytoskeletal Proteins
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Drosophila / growth & development
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Drosophila / metabolism
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Drosophila / physiology*
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Drosophila / ultrastructure
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Electric Stimulation / methods
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Endocytosis
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GTP Phosphohydrolases / isolation & purification
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GTP Phosphohydrolases / physiology
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GTP-Binding Proteins
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Larva
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mitochondria / metabolism
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Mitochondria / physiology*
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Mitochondria / ultrastructure
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Mutation
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Myosin Light Chains / metabolism
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Myosins / metabolism
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Neuromuscular Junction / metabolism
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Neuromuscular Junction / physiology*
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Neuromuscular Junction / ultrastructure
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Neuropeptides / genetics
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Neuropeptides / metabolism
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Neurotransmitter Agents / metabolism
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Presynaptic Terminals / metabolism
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Synapses / metabolism
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Synapses / physiology*
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Synaptic Transmission
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Synaptic Vesicles / physiology*
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Tissue Distribution
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Vesicular Transport Proteins
Substances
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Cytoskeletal Proteins
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Dap160 protein, Drosophila
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Drosophila Proteins
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Membrane Proteins
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Myosin Light Chains
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Neuropeptides
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Neurotransmitter Agents
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Vesicular Transport Proteins
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Cyclic AMP-Dependent Protein Kinases
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DRP1 protein, Drosophila
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GTP Phosphohydrolases
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GTP-Binding Proteins
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Myosins
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Calcium