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

Research output: Contribution to journalArticle

107 Citations (Scopus)

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
Externally publishedYes

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Glycogen Synthase Kinase 3
Neurofibrillary Tangles
Phosphorylation
COS Cells
MAP Kinase Kinase Kinases
Microtubule-Associated Proteins
Adenoviridae
Gene expression
Neurodegenerative Diseases
Detergents
Epitopes
Alzheimer Disease
Phosphotransferases
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sato, S., Tatebayashi, Y., Akagi, T., Chui, D. H., Murayama, M., Miyasaka, T., ... 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

Aberrant tau phosphorylation by glycogen synthase kinase-3β and JNK3 induces oligomeric tau fibrils in COS-7 cells. / Sato, Shinji; Tatebayashi, Yoshitaka; Akagi, Takumi; Chui, De Hua; Murayama, Miyuki; Miyasaka, Tomohiro; Planel, Emmanuel; Tanemura, Kentaro; Sun, Xiaoyan; Hashikawa, Tsutomu; Yoshioka, Katsuji; Ishiguro, Koichi; Takashima, Akihiko.

In: Journal of Biological Chemistry, Vol. 277, No. 44, 01.11.2002, p. 42060-42065.

Research output: Contribution to journalArticle

Sato, S, Tatebayashi, Y, Akagi, T, Chui, DH, 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, vol. 277, no. 44, pp. 42060-42065. https://doi.org/10.1074/jbc.M202241200
Sato, Shinji ; Tatebayashi, Yoshitaka ; Akagi, Takumi ; Chui, De Hua ; Murayama, Miyuki ; Miyasaka, Tomohiro ; Planel, Emmanuel ; Tanemura, Kentaro ; Sun, Xiaoyan ; Hashikawa, Tsutomu ; Yoshioka, Katsuji ; Ishiguro, Koichi ; Takashima, Akihiko. / Aberrant tau phosphorylation by glycogen synthase kinase-3β and JNK3 induces oligomeric tau fibrils in COS-7 cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 44. pp. 42060-42065.
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