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

Mei Zhang Dong Mei Zhang, D. Levitan, G. Yu, M. Nishimura, F. Chen, A. Tandon, T. Kawarai, S. Arawaka, A. Supala, Y. Q. Song, E. Rogaeva, Y. Liang, E. Holmes, P. Milman, C. Sato, L. Zhang, P. St George-Hyslop

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)3227-3230
Number of pages4
JournalNeuroReport
Volume11
Issue number14
DOIs
StatePublished - Oct 28 2000

Keywords

  • Alzheimer disease
  • Development
  • Notch
  • Presenilin
  • Sel-12
  • lin-12
  • β-amyloid precursor protein

ASJC Scopus subject areas

  • Neuroscience(all)

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    Dong Mei Zhang, M. Z., Levitan, D., Yu, G., Nishimura, M., Chen, F., Tandon, A., Kawarai, T., Arawaka, S., Supala, A., Song, Y. Q., Rogaeva, E., Liang, Y., Holmes, E., Milman, P., Sato, C., Zhang, L., & St George-Hyslop, P. (2000). 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. NeuroReport, 11(14), 3227-3230. https://doi.org/10.1097/00001756-200009280-00035