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Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go

Nature volume 362, pages 75–79 (1993)Cite this article

Abstract

THE most characteristic change in progressive dementia of Alzheimer's type is a tissue deposit of amyloid β/A4 protein1, which is derived from its precursor protein APP (ref. 2). Structural alterations of APP are implicated in the pathogenesis of Alzheimer's disease, but it is not known how they cause the disease. Although APP has a receptor-like architecture2–5, is located on the neuronal surface6, and has a conserved cytoplasmic domain7, no receptor function has been demonstrated for APP. Here we report that APP forms a complex with Go, a major GTP-binding protein in brain. The cytoplasmic APP sequence His 657–Lys 676 shows a specific Go-activating function and is necessary for complex formation. Go protein treated with GTP-γS lost the ability to associate with APP. This suggests that APP is a receptor coupled to Go and that abnormal APP–Go signalling is involved in the Alzheimer's disease process.

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Author notes

  1. Ikuo Nishimoto, Takashi Okamoto & Toshimi Okamoto

    Present address: Department of Medicine, Harvard Medical School, Cardiovascular Research Center, Massachusetts General Hospital-East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

  2. Etsuro Ogata

    Present address: Cancer Research Institute, 1-37-1 Kami-lkebukuro, Toshima-ku, Tokyo, 170, Japan

Authors and Affiliations

  1. Life Science Laboratory, Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo, 112, Japan

    Ikuo Nishimoto, Takashi Okamoto, Toshimi Okamoto, Yoshitake Murayama & Etsuro Ogata

  2. Laboratory of Hepatitis Viruses, Department of Virology II, National Institute of Health, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 160, Japan

    Yoshiharu Matsuura

  3. Department of Pathology, Sapporo Medical College, SI, W17, Chuo-ku, Sapporo, 060, Japan

    Shuji Takahashi

Authors
  1. Ikuo Nishimoto
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  2. Takashi Okamoto
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  4. Shuji Takahashi
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  6. Yoshitake Murayama
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  7. Etsuro Ogata
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Nishimoto, I., Okamoto, T., Matsuura, Y. et al. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature 362, 75–79 (1993). https://doi.org/10.1038/362075a0

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