Glutamine/Proline-Rich PQE-1 Proteins Protect Caenorhabditis elegans Neurons from Huntingtin Polyglutamine Neurotoxicity

Huntington's disease is a progressive neurodegenerative disease caused by a polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971-983]. To understand the mechanism by which polyQ repeats cause neurodegenerati...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-12, Vol.99 (26), p.17131-17136
Main Authors: Faber, Peter W., Voisine, Cindy, King, Daphne C., Bates, Emily A., Hart, Anne C.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Caenorhabditis elegans - drug effects
Caenorhabditis elegans - genetics
Cell death
Chromosome Mapping
Dyes
Genetic mutation
Helminth Proteins - genetics
Helminth Proteins - physiology
Huntington disease
Huntington Disease - etiology
Nervous system diseases
Neurological disorders
Neurology
Neurons
Neurons - drug effects
Neurotoxicity
Neurotoxicity Syndromes - prevention & control
Peptides - genetics
Peptides - physiology
Peptides - toxicity
Proline-Rich Protein Domains
Proteins
Transcription, Genetic
Transgenes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Huntington's disease is a progressive neurodegenerative disease caused by a polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971-983]. To understand the mechanism by which polyQ repeats cause neurodegeneration and cell death, we modeled polyQ neurotoxicity in Caenorhabditis elegans. In our model, expression of N-terminal fragments of human huntingtin causes polyQ-dependent degeneration of neurons. We conducted a genetic screen to identify proteins that protect neurons from the toxic effects of expanded polyQ tracts. Loss of polyQ enhancer-1 (pqe-1) gene function strongly and specifically exacerbates neurodegeneration and cell death, whereas overexpression of a pqe-1 cDNA protects C. elegans neurons from the toxic effects of expanded huntingtin fragments. A glutamine/proline-rich domain, along with a charged domain, is critical for PQE-1 protein function. Analysis of pqe-1 suggests that proteins exist that specifically protect neurons from the toxic effects of expanded polyQ disease proteins.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.262544899