QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

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

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03401v1 120/6/1134    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tóth, M. L. Articles by Vellai, T. Search for Related Content PubMed PubMed Citation Articles by Tóth, M. L. Articles by Vellai, T. Social Bookmarking                         What's this?

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

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Neuronal death by consumption

JCS 2007 120: 603. [Full Text]  

This article has been cited by other articles:

				I. Aladzsity, M. L. Toth, T. Sigmond, E. Szabo, B. Bicsak, J. Barna, A. Regos, L. Orosz, A. L. Kovacs, and T. Vellai Autophagy Genes unc-51 and bec-1 Are Required for Normal Cell Size in Caenorhabditis elegans Genetics, September 1, 2007; 177(1): 655 - 660. [Abstract] [Full Text] [PDF]