Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex
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- Lia Baki
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Philippe Marambaud
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Spiros Efthimiopoulos
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Anastasios Georgakopoulos
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Paul Wen
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Wen Cui
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Junichi Shioi
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Eduard Koo
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Masayuki Ozawa
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Victor L. Friedrich
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
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- Nikolaos K. Robakis
- Department of Psychiatry and Fishberg Research Center for Neurobiology and Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093; and Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan
書誌事項
- 公開日
- 2001-02-27
- DOI
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- 10.1073/pnas.041603398
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p> Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, binds directly to epithelial cadherin (E-cadherin). This binding is mediated by the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic sequence 604–615 of mature E-cadherin. This sequence is also required for E-cadherin binding of protein p120, a known regulator of cadherin-mediated cell adhesion. Using wild-type and PS1 knockout cells, we found that increasing PS1 levels suppresses p120/E-cadherin binding, and increasing p120 levels suppresses PS1/E-cadherin binding. Thus PS1 and p120 bind to and mutually compete for cellular E-cadherin. Furthermore, PS1 stimulates E-cadherin binding to β- and γ-catenin, promotes cytoskeletal association of the cadherin/catenin complexes, and increases Ca <jats:sup>2+</jats:sup> -dependent cell–cell aggregation. Remarkably, PS1 familial Alzheimer disease mutant ΔE9 increased neither the levels of cadherin/catenin complexes nor cell aggregation, suggesting that this familial Alzheimer disease mutation interferes with cadherin-based cell–cell adhesion. These data identify PS1 as an E-cadherin-binding protein and a regulator of E-cadherin function <jats:italic>in vivo</jats:italic> . </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 98 (5), 2381-2386, 2001-02-27
Proceedings of the National Academy of Sciences