Glial-derived prodegenerative signaling in the Drosophila neuromuscular system.

Lani C Keller, Ling Cheng, Cody J Locke, Martin Müller, Richard D Fetter, Graeme W Davis

Department of Biochemistry and Biophysics, University of California, San Francisco, 1550 4th Street, Rock Hall 4th Floor North, San Francisco, CA 94143, USA.

Neuron 2011 Dec 8

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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.

Citation

Lani C Keller, Ling Cheng, Cody J Locke, Martin Müller, Richard D Fetter, Graeme W Davis. Glial-derived prodegenerative signaling in the Drosophila neuromuscular system. Neuron. 2011 Dec 8;72(5):760-75