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

Biochem Biophys Res Commun. 1997 Sep 18;238(2):599-605. doi: 10.1006/bbrc.1997.7337.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Dimerization
  • Green Fluorescent Proteins
  • Luminescent Proteins / chemistry*
  • Luminescent Proteins / ultrastructure
  • Mice
  • Peptides / chemistry*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / ultrastructure


  • Luminescent Proteins
  • Peptides
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • polyglutamine