Aberrant tau phosphorylation by glycogen synthase kinase-3β and JNK3 induces oligomeric tau fibrils in COS-7 cells

Shinji Sato, Yoshitaka Tatebayashi, Takumi Akagi, De Hua Chui, Miyuki Murayama, Tomohiro Miyasaka, Emmanuel Planel, Kentaro Tanemura, Xiaoyan Sun, Tsutomu Hashikawa, Katsuji Yoshioka, Koichi Ishiguro, Akihiko Takashima

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Abstract

Neurofibrillary tangles (NFTs) are found in a wide range of neurodegenerative disorders, including Alzheimer's disease. The major component of NFTs is aberrantly hyperphosphorylated microtubule-associated protein tau. Because appropriate in vivo models have been lacking, the role of tau phosphorylation in NFTs formation has remained elusive. Here, we describe a new model in which adenovirus-mediated gene expression of tau, ΔMEKK, JNK3, and GSK-3β in COS-7 cells produces most of the pathological phosphorylation epitopes of tau including AT100. Furthermore, this co-expression resulted in the formation of tau aggregates having short fibrils that were detergent-insoluble and Thioflavin-S-reactive. These results suggest that aberrant tau phosphorylation by the combination of these kinases may be involved in "pretangle," oligomeric tau fibril formation in vivo.

Original languageEnglish (US)
Pages (from-to)42060-42065
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number44
DOIs
StatePublished - Nov 1 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sato, S., Tatebayashi, Y., Akagi, T., Chui, D. H., Murayama, M., Miyasaka, T., Planel, E., Tanemura, K., Sun, X., Hashikawa, T., Yoshioka, K., Ishiguro, K., & Takashima, A. (2002). Aberrant tau phosphorylation by glycogen synthase kinase-3β and JNK3 induces oligomeric tau fibrils in COS-7 cells. Journal of Biological Chemistry, 277(44), 42060-42065. https://doi.org/10.1074/jbc.M202241200