Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network.
Eight inherited neurodegenerative diseases are caused by genes with expanded CAG repeats coding for polyglutamine domains in the disease-producing proteins. The mechanism by which this expanded polyglutamine domain causes neurodegenerative disease is unknown, but nuclear and cytoplasmic polyglutamine protein aggregation is a common feature. In transfected COS7 cells, expanded polyglutamine proteins aggregate and disrupt the vimentin intermediate filament network. Since neurons have an intermediate filament network composed of neurofilament (NF) and NF abnormalities occur in neurodegenerative diseases, we examined whether pathologic-length polyglutamine domain proteins also interact with NF. We expressed varying lengths polyglutamine-green fluorescent protein fusion proteins in a neuroblast cell line, TR1. Pathologic-length polyglutamine-GFP fusion proteins formed large cytoplasmic aggregates surrounded by neurofilament. Immunoisolation of pathologic-length polyglutamine proteins coisolated 68-kDa NF protein demonstrating molecular interaction. These observations suggest that polyglutamine interaction with NF is important in the pathogenesis of the polyglutamine repeat diseases.
Duke Scholars
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- Tumor Cells, Cultured
- Transfection
- Repetitive Sequences, Nucleic Acid
- Recombinant Fusion Proteins
- Protein Binding
- Peptides
- Neurons
- Neurology & Neurosurgery
- Neurofilament Proteins
- Neurodegenerative Diseases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Transfection
- Repetitive Sequences, Nucleic Acid
- Recombinant Fusion Proteins
- Protein Binding
- Peptides
- Neurons
- Neurology & Neurosurgery
- Neurofilament Proteins
- Neurodegenerative Diseases