Article: Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes

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TitleMutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes
AuthorsYu, G2 3
Chen, F2 3
Nishimura, M2 3
Steiner, H1
Tandon, A2 3
Kawarai, T2 3
Arawaka, S2 3
Supala, A2 3
Song, YQ2 3
Rogaeva, E2 3
Holmes, E2 3
Zhang, DM2 3
Milman, P2 3
Fraser, PE2 3
Haass, C1
St GeorgeHyslop, P2 3
Issue Date2000
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2000, v. 275 n. 35, p. 27348-27353 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M002982200
AbstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments. Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of β-amyloid precursor protein and Notch. We show that although PS1/PS2 endoproteolysis is not required for inclusion into the higher MW N- and C-terminal fragment-containing complex, aspartate mutant holoprotein presenilins are not incorporated into the high MW complexes. Aspartate mutant presenilin holoproteins also preclude entry of endogenous wild type PS1/PS2 into the high MW complexes but do not affect the incorporation of wild type holoproteins into lower MW holoprotein complexes. These data suggest that the loss of function effects of the aspartate mutants results in altered PS complex maturation and argue that the functional presenilin moieties are contained in the high molecular weight complexes.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M002982200
ISI Accession Number IDWOS:000089144800091
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYu, G
dc.contributor.authorChen, F
dc.contributor.authorNishimura, M
dc.contributor.authorSteiner, H
dc.contributor.authorTandon, A
dc.contributor.authorKawarai, T
dc.contributor.authorArawaka, S
dc.contributor.authorSupala, A
dc.contributor.authorSong, YQ
dc.contributor.authorRogaeva, E
dc.contributor.authorHolmes, E
dc.contributor.authorZhang, DM
dc.contributor.authorMilman, P
dc.contributor.authorFraser, PE
dc.contributor.authorHaass, C
dc.contributor.authorSt GeorgeHyslop, P
dc.date.accessioned2011-07-14T07:02:57Z
dc.date.available2011-07-14T07:02:57Z
dc.date.issued2000
dc.description.abstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments. Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of β-amyloid precursor protein and Notch. We show that although PS1/PS2 endoproteolysis is not required for inclusion into the higher MW N- and C-terminal fragment-containing complex, aspartate mutant holoprotein presenilins are not incorporated into the high MW complexes. Aspartate mutant presenilin holoproteins also preclude entry of endogenous wild type PS1/PS2 into the high MW complexes but do not affect the incorporation of wild type holoproteins into lower MW holoprotein complexes. These data suggest that the loss of function effects of the aspartate mutants results in altered PS complex maturation and argue that the functional presenilin moieties are contained in the high molecular weight complexes.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2000, v. 275 n. 35, p. 27348-27353 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M002982200
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M002982200
dc.identifier.epage27353
dc.identifier.isiWOS:000089144800091
dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue35
dc.identifier.pmid10856299
dc.identifier.scopuseid_2-s2.0-0034282749
dc.identifier.spage27348
dc.identifier.urihttp://hdl.handle.net/10722/134762
dc.identifier.volume275
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.subject.meshAspartic Acid/*genetics
dc.subject.meshCell Line
dc.subject.meshHumans
dc.subject.meshMembrane Proteins/genetics/*physiology
dc.subject.meshMutagenesis
dc.subject.meshPresenilin-1
dc.subject.meshPresenilin-2
dc.subject.meshProtein Processing, Post-Translational
dc.titleMutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes
dc.typeArticle
Author Affiliations
  1. Adolf-Butenandt-Institut
  2. Toronto Western Hospital
  3. University of Toronto