Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Nagai, Y; Onodera, O; Chun, J; Strittmatter, WJ; Burke, JR

Published Date

  • February 1999

Published In

Volume / Issue

  • 155 / 2

Start / End Page

  • 195 - 203

PubMed ID

  • 10072295

International Standard Serial Number (ISSN)

  • 0014-4886

Digital Object Identifier (DOI)

  • 10.1006/exnr.1998.6991


  • eng

Conference Location

  • United States