| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Alzheimer's disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Aβ secretion : role for altered lysosomal hydrolase distribution in β-amyloidogenesis |
| Autor/-in: | Mathews, Paul M. Guerra, Carolyn B. Jiang, Ying Grbovic, Olivera M. Kao, Benjamin H. Schmidt, Stephen D. Dinakar, Ravi Mercken, Marc Hille-Rehfeld, Annette Rohrer, Jack Mehta, Pankaj Cataldo, Anne M. Nixon, Ralph A. |
| DOI: | 10.1074/jbc.M108161200 |
| Erschienen in: | Journal of Biological Chemistry |
| Band(Heft): | 277 |
| Heft: | 7 |
| Seite(n): | 5299 |
| Seiten bis: | 5307 |
| Erscheinungsdatum: | 10-Sep-2002 |
| Verlag / Hrsg. Institution: | American Society for Biochemistry and Molecular Biology |
| ISSN: | 1083-351X |
| Sprache: | Englisch |
| Fachgebiet (DDC): | 571: Physiologie und verwandte Themen 572: Biochemie |
| Zusammenfassung: | Prominent endosomal and lysosomal changes are an invariant feature of neurons in sporadic Alzheimer's disease (AD). These changes include increased levels of lysosomal hydrolases in early endosomes and increased expression of the cation-dependent mannose 6-phosphate receptor (CD-MPR), which is partially localized to early endosomes. To determine whether AD-associated redistribution of lysosomal hydrolases resulting from changes in CD-MPR expression affects amyloid precursor protein (APP) processing, we stably transfected APP-overexpressing murine L cells with human CD-MPR. As controls for these cells, we also expressed CD-MPR trafficking mutants that either localize to the plasma membrane (CD-MPRpm) or to early endosomes (CD-MPRendo). Expression of CD-MPR resulted in a partial redistribution of a representative lysosomal hydrolase, cathepsin D, to early endosomal compartments. Turnover of APP and secretion of sAPPalpha and sAPPbeta were not altered by overexpression of any of the CD-MPR constructs. However, secretion of both human Abeta40 and Abeta42 into the growth media nearly tripled in CD-MPR- and CD-MPRendo-expressing cells when compared with parental or CD-MPRpm-expressing cells. Comparable increases were confirmed for endogenous mouse Abeta40 in L cells expressing these CD-MPR constructs but not overexpressing human APP. These data suggest that redistribution of lysosomal hydrolases to early endocytic compartments mediated by increased expression of the CD-MPR may represent a potentially pathogenic mechanism for accelerating Abeta generation in sporadic AD, where the mechanism of amyloidogenesis is unknown. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/6807 |
| Volltext Version: | Publizierte Version |
| Lizenz (gemäss Verlagsvertrag): | Lizenz gemäss Verlagsvertrag |
| Departement: | Life Sciences und Facility Management |
| Organisationseinheit: | Institut für Chemie und Biotechnologie (ICBT) |
| Enthalten in den Sammlungen: | Publikationen Life Sciences und Facility Management |
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Mathews, P. M., Guerra, C. B., Jiang, Y., Grbovic, O. M., Kao, B. H., Schmidt, S. D., Dinakar, R., Mercken, M., Hille-Rehfeld, A., Rohrer, J., Mehta, P., Cataldo, A. M., & Nixon, R. A. (2002). Alzheimer’s disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Aβ secretion : role for altered lysosomal hydrolase distribution in β-amyloidogenesis. Journal of Biological Chemistry, 277(7), 5299–5307. https://doi.org/10.1074/jbc.M108161200
Mathews, P.M. et al. (2002) ‘Alzheimer’s disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Aβ secretion : role for altered lysosomal hydrolase distribution in β-amyloidogenesis’, Journal of Biological Chemistry, 277(7), pp. 5299–5307. Available at: https://doi.org/10.1074/jbc.M108161200.
P. M. Mathews et al., “Alzheimer’s disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Aβ secretion : role for altered lysosomal hydrolase distribution in β-amyloidogenesis,” Journal of Biological Chemistry, vol. 277, no. 7, pp. 5299–5307, Sep. 2002, doi: 10.1074/jbc.M108161200.
MATHEWS, Paul M., Carolyn B. GUERRA, Ying JIANG, Olivera M. GRBOVIC, Benjamin H. KAO, Stephen D. SCHMIDT, Ravi DINAKAR, Marc MERCKEN, Annette HILLE-REHFELD, Jack ROHRER, Pankaj MEHTA, Anne M. CATALDO und Ralph A. NIXON, 2002. Alzheimer’s disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Aβ secretion : role for altered lysosomal hydrolase distribution in β-amyloidogenesis. Journal of Biological Chemistry. 10 September 2002. Bd. 277, Nr. 7, S. 5299–5307. DOI 10.1074/jbc.M108161200
Mathews, Paul M., Carolyn B. Guerra, Ying Jiang, Olivera M. Grbovic, Benjamin H. Kao, Stephen D. Schmidt, Ravi Dinakar, et al. 2002. “Alzheimer’s Disease-Related Overexpression of the Cation-Dependent Mannose 6-Phosphate Receptor Increases Aβ Secretion : Role for Altered Lysosomal Hydrolase Distribution in β-Amyloidogenesis.” Journal of Biological Chemistry 277 (7): 5299–5307. https://doi.org/10.1074/jbc.M108161200.
Mathews, Paul M., et al. “Alzheimer’s Disease-Related Overexpression of the Cation-Dependent Mannose 6-Phosphate Receptor Increases Aβ Secretion : Role for Altered Lysosomal Hydrolase Distribution in β-Amyloidogenesis.” Journal of Biological Chemistry, vol. 277, no. 7, Sept. 2002, pp. 5299–307, https://doi.org/10.1074/jbc.M108161200.
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