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Updated: May 10, 2026

Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates
Wen-Juan Guan1, Kai-De Xia, Yan-Tao Ma
1Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Abstract:
A common feature of polyglutamine (polyQ) diseases is the presence of aggregates in neuronal cells caused by expanded polyglutamine tracts. PolyQ proteins are the substrates of transglutaminase 2, and the increased activity of transglutaminase in polyQ diseases suggests that transglutaminase may be directly involved in the formation of the aggregates. We previously identified the transglutaminase 6 gene to be causative of spinocerebellar ataxia type 35 (SCA35), and we found that SCA35-associated mutants exhibited reduced transglutaminase activity. Here we report that transglutaminase 6 interacts and co-localizes with both normal and expanded polyQ proteins in HEK293 cells. Moreover, the overexpression of transglutaminase 6 promotes the formation of polyQ aggregates and the conversion of soluble polyQ into insoluble polyQ aggregates. However, SCA35-associated mutants do not affect their interactions with polyQ proteins. These data suggest that transglutaminase 6 could be involved in polyQ diseases and there may exist a common pathological link between polyQ associated SCA and SCA35.
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