Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS

Inukai, Yuki; Nonaka, Takashi; Arai, Tetsuaki; Yoshida, Mari; Hashizume, Yoshio; Beach, Thomas G.; Buratti, Emanuele; Baralle, Francisco E.; Akiyama, Haruhiko; Hisanaga, Shin-ichi; Hasegawa, Masato

doi:10.1016/j.febslet.2008.07.027

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Volume 582, Issue 19 , Pages 2899-2904, 20 August 2008

Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS

Edited by Jesus Avila

Yuki Inukai
- Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
- Molecular Neuroscience Laboratory, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan
Takashi Nonaka
- Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Tetsuaki Arai
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Mari Yoshida
- Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 21 Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan
Yoshio Hashizume
- Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 21 Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan
Thomas G. Beach
- Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, United States
Emanuele Buratti
- International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy
Francisco E. Baralle
- International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy
Haruhiko Akiyama
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Shin-ichi Hisanaga
- Molecular Neuroscience Laboratory, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan
Masato Hasegawa
- Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
- Corresponding author. Fax: +81 3 3329 8035.

Received 18 June 2008; received in revised form 9 July 2008; accepted 14 July 2008. published online 24 July 2008.

Abstract

A monoclonal antibody specific for phosphoserines 409 and 410 of TDP-43 (mAb pS409/410) has been produced. It strongly stained TDP-43-positive inclusions in brain of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis, but did not stain nuclei, in which normal TDP-43 is localized. It did not recognize TDP-43 rapidly extracted from brains of rats at various developmental stages, strongly suggesting that phosphorylation of Ser409/410 is an abnormal event. Analysis of postmortem changes of TDP-43 revealed that the amounts of Sarkosyl-insoluble, urea-soluble full-length TDP-43 and a 35kDa N-terminal fragment increased time-dependently.