Article: Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased Aβ42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans

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TitleMutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased Aβ42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans
AuthorsDong Mei Zhang1
Levitan, D1
Yu, G1
Nishimura, M1
Chen, F1
Tandon, A1
Kawarai, T1
Arawaka, S1
Supala, A1
Song, YQ1
Rogaeva, E1
Liang, Y1
Holmes, E1
Milman, P1
Sato, C1
Zhang, L1
St GeorgeHyslop, P1
Keywordsβ-amyloid precursor protein
Aβ
Alzheimer disease
Development
lin-12
Notch
Presenilin
Sel-12
Issue Date2000
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neuroreport.com
CitationNeuroreport, 2000, v. 11 n. 14, p. 3227-3230 [How to Cite?]
AbstractThe presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the β-amyloid precursor protein (βAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase γ-secretase cleavage of βAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased Aβ42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and βAPP processing are either separately regulated activities or independent activities of the presenilins. (C) 2000 Lippincott Williams and Wilkins.
ISSN0959-4965
2011 Impact Factor: 1.656
2011 SCImago Journal Rankings: 0.146
ISI Accession Number IDWOS:000089833500036
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorDong Mei Zhang
dc.contributor.authorLevitan, D
dc.contributor.authorYu, G
dc.contributor.authorNishimura, M
dc.contributor.authorChen, F
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.authorLiang, Y
dc.contributor.authorHolmes, E
dc.contributor.authorMilman, P
dc.contributor.authorSato, C
dc.contributor.authorZhang, L
dc.contributor.authorSt GeorgeHyslop, P
dc.date.accessioned2011-07-14T07:03:07Z
dc.date.available2011-07-14T07:03:07Z
dc.date.issued2000
dc.description.abstractThe presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the β-amyloid precursor protein (βAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase γ-secretase cleavage of βAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased Aβ42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and βAPP processing are either separately regulated activities or independent activities of the presenilins. (C) 2000 Lippincott Williams and Wilkins.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNeuroreport, 2000, v. 11 n. 14, p. 3227-3230 [How to Cite?]
dc.identifier.epage3230
dc.identifier.isiWOS:000089833500036
dc.identifier.issn0959-4965
2011 Impact Factor: 1.656
2011 SCImago Journal Rankings: 0.146
dc.identifier.issue14
dc.identifier.pmid11043553
dc.identifier.scopuseid_2-s2.0-0034727409
dc.identifier.spage3227
dc.identifier.urihttp://hdl.handle.net/10722/134766
dc.identifier.volume11
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neuroreport.com
dc.publisher.placeUnited States
dc.relation.ispartofNeuroReport
dc.relation.referencesReferences in Scopus
dc.subject.meshAmyloid beta-Peptides/*genetics/metabolism
dc.subject.meshAnimals
dc.subject.meshCaenorhabditis elegans/*genetics/metabolism
dc.subject.mesh*Caenorhabditis elegans Proteins
dc.subject.meshCysteine/*genetics
dc.subject.meshHelminth Proteins/genetics/*metabolism
dc.subject.meshHumans
dc.subject.meshMembrane Proteins/*genetics/*metabolism
dc.subject.meshMutation, Missense/physiology
dc.subject.meshPeptide Fragments/*genetics/metabolism
dc.subject.meshPoint Mutation/genetics
dc.subject.meshPresenilin-1
dc.subject.meshProtein Structure, Tertiary/genetics
dc.subject.meshReceptors, Notch
dc.subject.meshSignal Transduction/genetics
dc.subjectβ-amyloid precursor protein
dc.subjectAβ
dc.subjectAlzheimer disease
dc.subjectDevelopment
dc.subjectlin-12
dc.subjectNotch
dc.subjectPresenilin
dc.subjectSel-12
dc.titleMutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased Aβ42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans
dc.typeArticle
Author Affiliations
  1. University Health Network