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Article: Metabolism of the 'Swedish' amyloid precursor protein variant in Madin- Darby canine kidney cells

TitleMetabolism of the 'Swedish' amyloid precursor protein variant in Madin- Darby canine kidney cells
Authors
Issue Date1994
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1994, v. 269 n. 49, p. 30966-30973 How to Cite?
AbstractThe 4-kDa β-amyloid peptide (Aβ), a major constituent of parenchymal amyloid deposits in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). We have examined the metabolism of APP in Madin- Darby canine kidney cells stably transfected with cDNA encoding either wild- type human APP-695 or human APP-695 that harbors the Swedish double mutation associated with familial early-onset Alzheimer's disease. Although ~90% of total soluble APP secreted from wild-type cells is secreted basolaterally following cleavage at the α-secretase site, soluble derivatives cleaved near or at the amino terminus of Aβ (presumably the 'β-secretase' site) are preferentially secreted into the apical compartment of SWE cells. Concomitantly, levels of a specific Aβ-containing carboxyl-terminal fragment are elevated in SWE cell lysates. Using domain-specific biotinylation and release assays, we failed to detect a β-secretase-generated soluble derivative (APP(sβ)) released from the surface of SWE cells. However, APP(sβ) can be detected in SWE cell lysates, consistent with 'β-secretase' cleavage occurring in an intracellular compartment. Finally, we demonstrate that Aβ is secreted into the basolateral compartment of SWE cells and that the majority of these Aβ-related species contains an amino-terminal aspartate residue (+1).
Persistent Identifierhttp://hdl.handle.net/10722/176339
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLo, ACYen_US
dc.contributor.authorHaass, Cen_US
dc.contributor.authorWagner, SLen_US
dc.contributor.authorTeplow, DBen_US
dc.contributor.authorSisodia, SSen_US
dc.date.accessioned2012-11-26T09:10:40Z-
dc.date.available2012-11-26T09:10:40Z-
dc.date.issued1994en_US
dc.identifier.citationJournal Of Biological Chemistry, 1994, v. 269 n. 49, p. 30966-30973en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/176339-
dc.description.abstractThe 4-kDa β-amyloid peptide (Aβ), a major constituent of parenchymal amyloid deposits in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). We have examined the metabolism of APP in Madin- Darby canine kidney cells stably transfected with cDNA encoding either wild- type human APP-695 or human APP-695 that harbors the Swedish double mutation associated with familial early-onset Alzheimer's disease. Although ~90% of total soluble APP secreted from wild-type cells is secreted basolaterally following cleavage at the α-secretase site, soluble derivatives cleaved near or at the amino terminus of Aβ (presumably the 'β-secretase' site) are preferentially secreted into the apical compartment of SWE cells. Concomitantly, levels of a specific Aβ-containing carboxyl-terminal fragment are elevated in SWE cell lysates. Using domain-specific biotinylation and release assays, we failed to detect a β-secretase-generated soluble derivative (APP(sβ)) released from the surface of SWE cells. However, APP(sβ) can be detected in SWE cell lysates, consistent with 'β-secretase' cleavage occurring in an intracellular compartment. Finally, we demonstrate that Aβ is secreted into the basolateral compartment of SWE cells and that the majority of these Aβ-related species contains an amino-terminal aspartate residue (+1).en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAmyloid Precursor Protein Secretasesen_US
dc.subject.meshAmyloid Beta-Protein Precursor - Genetics - Metabolism - Secretionen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAspartic Acid - Chemistryen_US
dc.subject.meshAspartic Acid Endopeptidasesen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDogsen_US
dc.subject.meshEndopeptidases - Metabolismen_US
dc.subject.meshHydrolysisen_US
dc.subject.meshKidney - Cytology - Enzymology - Metabolismen_US
dc.subject.meshKineticsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshOligodeoxyribonucleotidesen_US
dc.subject.meshSubcellular Fractions - Enzymologyen_US
dc.titleMetabolism of the 'Swedish' amyloid precursor protein variant in Madin- Darby canine kidney cellsen_US
dc.typeArticleen_US
dc.identifier.emailLo, ACY: amylo@hkucc.hku.hken_US
dc.identifier.authorityLo, ACY=rp00425en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid7983032-
dc.identifier.scopuseid_2-s2.0-0028172238en_US
dc.identifier.volume269en_US
dc.identifier.issue49en_US
dc.identifier.spage30966en_US
dc.identifier.epage30973en_US
dc.identifier.isiWOS:A1994PV51000038-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLo, ACY=7102780640en_US
dc.identifier.scopusauthoridHaass, C=7006070304en_US
dc.identifier.scopusauthoridWagner, SL=7402232858en_US
dc.identifier.scopusauthoridTeplow, DB=7006828349en_US
dc.identifier.scopusauthoridSisodia, SS=7102763509en_US

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