Tissue transglutaminase does not contribute to the formation of mutant huntingtin aggregates

Wanjoo Chun, Mathieu Lesort, Janusz Tucholski, Christopher A. Ross, Gail V.W. Johnson

Research output: Contribution to journalArticlepeer-review


The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the NH2-terminal region of huntingtin. Neuronal intranuclear inclusions and cytoplasmic aggregates composed of the mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because in vitro expanded polyglutamine repeats are glutaminyl-donor substrates of tissue transglutaminase (tTG), it has been hypothesized that tTG may contribute to the formation of these aggregates in HD. Therefore, it is of fundamental importance to establish whether tTG plays a significant role in the formation of mutant huntingtin aggregates in the cell. Human neuroblastoma SH-SY5Y cells were stably transfected with truncated NH2-terminal huntingtin constructs containing 18 (wild type) or 82 (mutant) glutamines. In the cells expressing the mutant truncated huntingtin construct, numerous SDS-resistant aggregates were present in the cytoplasm and nucleus. Even though numerous aggregates were present in the mutant huntingtin-expressing cells, tTG did not coprecipitate with mutant truncated huntingtin. Further, tTG was totally excluded from the aggregates, and significantly increasing tTG expression had no effect on the number of aggregates or their intracellular localization (cytoplasm or nucleus). When a YFP-tagged mutant truncated huntingtin construct was transiently transfected into cells that express no detectable tTG due to stable transfection with a tTG antisense construct, there was extensive aggregate formation. These findings clearly demonstrate that tTG is not required for aggregate formation, and does not facilitate the process of aggregate formation. Therefore, in HD, as well as in other polyglutamine diseases, tTG is unlikely to play a role in the formation of aggregates.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalJournal of Cell Biology
Issue number1
StatePublished - Apr 2 2001


  • Huntington's disease
  • Inclusions
  • Isopeptide bond
  • Polar zipper
  • Polyglutamine

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Tissue transglutaminase does not contribute to the formation of mutant huntingtin aggregates'. Together they form a unique fingerprint.

Cite this