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

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

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	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
Authors:	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
Published in:	Journal of Biological Chemistry
Volume(Issue):	277
Issue:	7
Page(s):	5299
Pages to:	5307
Issue Date:	10-Sep-2002
Publisher / Ed. Institution:	American Society for Biochemistry and Molecular Biology
ISSN:	1083-351X
Language:	English
Subject (DDC):	571: Physiology and related subjects 572: Biochemistry
Abstract:	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
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	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.