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First published online 27 February 2007
doi: 10.1242/jcs.03401

Journal of Cell Science 120, 1134-1141 (2007)
Published by The Company of Biologists 2007
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Research Article

Influence of autophagy genes on ion-channel-dependent neuronal degeneration in Caenorhabditis elegans

Márton L. Tóth1, Péter Simon1, Attila L. Kovács2 and Tibor Vellai1,*

1 Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary
2 Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, H-1117, Hungary

* Author for correspondence (e-mail: vellai{at}falco.elte.hu)

Accepted 10 January 2007

Necrotic cell death is a common feature in numerous human neurodegenerative disorders. In the nematode Caenorhabditis elegans, gain-of-function mutations in genes that encode specific ion channel subunits such as the degenerins DEG-1 and MEC-4, and the acetylcholine receptor subunit DEG-3 lead to necrotic-like degeneration of a subset of neurons. Neuronal demise caused by ion channel hyperactivity is accompanied by intense degradation of cytoplasmic contents, dramatic membrane infolding and vacuole formation; however, the cellular pathways underlying such processes remain largely unknown. Here we show that the function of three autophagy genes, whose yeast and mammalian orthologs are implicated in cytoplasmic self-degradation, membrane trafficking and the cellular response to starvation, contributes to ion-channel-dependent neurotoxicity in C. elegans. Inactivation of unc-51, bec-1 and lgg-1, the worm counterparts of the yeast autophagy genes Atg1, Atg6 and Atg8 respectively, partially suppresses degeneration of neurons with toxic ion channel variants. We also demonstrate that the TOR-kinase-mediated signaling pathway, a nutrient sensing system that downregulates the autophagy gene cascade, protects neurons from undergoing necrotic cell death, whereas nutrient deprivation promotes necrosis. Our findings reveal a role for autophagy genes in neuronal cell loss in C. elegans.

Key words: Neurodegeneration, Ion channel subunits, Autophagy, C. elegans, Dopamine neurons, TOR signaling


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[Abstract] [Full Text] [PDF]


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