Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.

Journal Article (Journal Article)

Six inherited neurologic diseases, including Huntington's disease, result from the expansion of a CAG domain of the disease genes to produce a domain of more than 40 glutamines in the expressed protein. The mechanism by which expansion of this polyglutamine domain causes disease is unknown. Recent studies demonstrated oligomerization of polyglutamine-domain proteins in mammalian neurons. To study oligomerization of polyglutamine proteins and to identify heterologous protein interactions, varying length polyglutamine-green fluorescent protein fusion proteins were expressed in cultured COS-7 cells. The 19- and 35-glutamine fusion proteins (non-pathologic length) distributed diffusely throughout the cytoplasm. In contrast, 56- and 80-glutamine fusion proteins (pathologic length) formed fibrillar arrays resembling those previously observed in neurons in Huntington's disease and in a transgenic mouse model. These aggregates were intranuclear and intracytoplasmic. Intracytoplasmic aggregates were surrounded by collapsed intermediate filaments. The intermediate filament protein vimentin co-immunoisolated with expanded polyglutamine fusion proteins. This cellular model will expedite investigations into oligomerization of polyglutamine proteins and their interactions with other proteins.

Full Text

Duke Authors

Cited Authors

  • Onodera, O; Burke, JR; Miller, SE; Hester, S; Tsuji, S; Roses, AD; Strittmatter, WJ

Published Date

  • September 18, 1997

Published In

Volume / Issue

  • 238 / 2

Start / End Page

  • 599 - 605

PubMed ID

  • 9299559

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1997.7337


  • eng

Conference Location

  • United States