title: Glial-derived prodegenerative signaling in the Drosophila neuromuscular system.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, 1550 4th Street, Rock Hall 4th Floor North, San Francisco, CA 94143, USA.
authors.forename: Lani C
authors.initials: LC
authors.lastname: Keller
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Locke
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Richard D
authors.initials: RD
authors.lastname: Fetter
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; C464933:wgn protein, Drosophila; C070138:Ets97D protein, Drosophila; D049452:Green Fluorescent Proteins; D020169:Caspases; C103568:Dcp-1 protein, Drosophila