Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains

Sasaki, Kumi; Shimura, Hideki; Itaya, Masako; Tanaka, Ryota; Mori, Hideo; Mizuno, Yoshikuni; Kosik, Kenneth S.; Tanaka, Shigeki; Hattori, Nobutaka

doi:10.1016/j.febslet.2009.06.015

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Volume 583, Issue 13 , Pages 2194-2200, 7 July 2009

Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains

Edited by Jesus Avila

Kumi Sasaki
- Department of Neurology, Juntendo University Urayasu Hospital, Japan
- Institute for Environment and Gender Specific Medicine, Japan
Hideki Shimura
- Department of Neurology, Juntendo University Urayasu Hospital, Japan
- Institute for Environment and Gender Specific Medicine, Japan
Masako Itaya
- Juntendo University School of Medicine, Japan
Ryota Tanaka
- Department of Neurology, Juntendo University Urayasu Hospital, Japan
Hideo Mori
- Juntendo University Koshigaya Hospital, Japan
Yoshikuni Mizuno
- Juntendo University Koshigaya Hospital, Japan
Kenneth S. Kosik
- Neuroscience Research Institute, University of California, USA
Shigeki Tanaka
- Department of Neurology, Juntendo University Urayasu Hospital, Japan
Nobutaka Hattori
- Juntendo University School of Medicine, Japan
- Corresponding author. Address: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Fax: +81 3 58000547.

Received 7 May 2009; received in revised form 2 June 2009; accepted 5 June 2009. published online 15 June 2009.

Abstract

Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies.

Structured summary

MINT-7148349, MINT-7148361:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by pull-down (MI:0096)

MINT-7148372, MINT-7148384:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: AD, Alzheimer’s disease, PSP, progressive supranuclear palsy, CBD, corticobasal degeneration, EAAT2, excitatory amino acid transporter 2, NFTs, neurofibrillary tangles, GSK-3β, glycogen synthase kinase-3β, p-tau, phosphorylated tau, GLT1, glutamate transporter.