Abstract
We provide evidence for a prodegenerative, glial-derived signaling framework in the Drosophila neuromuscular system that includes caspase and mitochondria-dependent signaling. We demonstrate that Drosophila TNF-α (eiger) is expressed in a subset of peripheral glia, and the TNF-α receptor (TNFR), Wengen, is expressed in motoneurons. NMJ degeneration caused by disruption of the spectrin/ankyrin skeleton is suppressed by an eiger mutation or by eiger knockdown within a subset of peripheral glia. Loss of wengen in motoneurons causes a similar suppression providing evidence for glial-derived prodegenerative TNF-α signaling. Neither JNK nor NFκβ is required for prodegenerative signaling. However, we provide evidence for the involvement of both an initiator and effector caspase, Dronc and Dcp-1, and mitochondrial-dependent signaling. Mutations that deplete the axon and nerve terminal of mitochondria suppress degeneration as do mutations in Drosophila Bcl-2 (debcl), a mitochondria-associated protein, and Apaf-1 (dark), which links mitochondrial signaling with caspase activity in other systems.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Genetically Modified
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Apoptotic Protease-Activating Factor 1 / genetics
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Apoptotic Protease-Activating Factor 1 / metabolism
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Caspases / genetics
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Caspases / metabolism
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Disease Models, Animal
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Drosophila
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Excitatory Postsynaptic Potentials / genetics
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Fluorescence Recovery After Photobleaching / methods
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Green Fluorescent Proteins / genetics
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Mitochondria / genetics
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Mitochondria / metabolism
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Mitochondria / pathology
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Mitochondria / ultrastructure
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Motor Neuron Disease / genetics
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Motor Neuron Disease / pathology*
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Mutation / genetics
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Nerve Degeneration / genetics
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Nerve Degeneration / pathology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuroglia / physiology*
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Neuroglia / ultrastructure
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Neuromuscular Junction / genetics
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Neuromuscular Junction / metabolism
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Neuromuscular Junction / pathology*
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Neuromuscular Junction / ultrastructure
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA Interference / physiology
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism
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Signal Transduction / genetics
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Signal Transduction / physiology*
Substances
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Apoptotic Protease-Activating Factor 1
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Drosophila Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins
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Receptors, Tumor Necrosis Factor
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wgn protein, Drosophila
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Ets97D protein, Drosophila
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Green Fluorescent Proteins
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Caspases
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Dcp-1 protein, Drosophila