https://scholars.lib.ntu.edu.tw/handle/123456789/470036
Title: | Caveolin-1 Regulates γ-Secretase-Mediated AβPP Processing by Modulating Spatial Distribution of γ-Secretase in Membrane | Authors: | Kapoor A. WEN-MING HSU Wang B.-J. Wu G.-H. Lin T.-Y. Lee S.-J. Yen C.-T. Liang S.-M. Liao Y.-F. |
Issue Date: | 2010 | Publisher: | IOS Press | Journal Volume: | 22 | Journal Issue: | 2 | Start page/Pages: | 423-442 | Source: | Journal of Alzheimer's Disease | Abstract: | Amyloidogenic processing of amyloid-β precursor protein (AβPP) is associated with cholesterol- and sphingolipid-rich lipid rafts. Caveolin-1, a raft-residing protein, has been implicated in the pathogenesis of Alzheimer's disease. To determine the role of caveolin-1 in governing γ-secretase- mediated AβPP proteolysis, cellular γ-secretase activity was assessed in response to alteration in caveolin-1 expression. We demonstrated that suppression of caveolin-1 expression by RNA interference resulted in a significant increase in γ-secretase-mediated proteolysis of AβPP, generation of amyloid-β, and cleavage of Notch. Overexpression of caveolin-1 attenuated γ-secretase-mediated proteolysis of AβPP and Notch, substantiating the negative regulation of γ-secretase by caveolin-1. Furthermore, we found that cells deficient in caveolin-1 exhibited significantly increased co-localization of γ-secretase with clathrin-coated non-caveolar endocytic vesicles, demonstrating that the partitioning of γ-secretase between caveolar and non-caveolar membranes can be modulated by caveolin-1. Our data also showed that JNK activation is essential for caveolin-1-mediated regulation of γ-secretase. Together, our results strongly suggest that caveolin-1 is an important regulator of γ-secretase activity. ? 2010 - IOS Press and the authors. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650848737&doi=10.3233%2fJAD-2010-100531&partnerID=40&md5=93d941c015ab191301c5695629ae6bd7 https://scholars.lib.ntu.edu.tw/handle/123456789/470036 |
ISSN: | 1387-2877 | DOI: | 10.3233/JAD-2010-100531 | SDG/Keyword: | amyloid precursor protein; beta secretase; caveolin 1; gamma secretase; Janus kinase; Notch receptor; article; cell fractionation; clinical assessment; coated vesicle; down regulation; enzyme activity; enzyme regulation; human; human cell; intracellular signaling; priority journal; protein degradation; protein expression; protein localization; protein protein interaction; RNA interference |
Appears in Collections: | 醫學系 |
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