The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms

Xuefeng Xia, Pei Wang, Xiaoyan Sun, Salvador Soriano, Wan Kyng Shum, Haruyasu Yamaguchi, Myrna E. Trumbauer, Akihiko Takashima, Edward H. Koo, Hui Zheng

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

To differentiate multiple activities of presenilin 1 (PS1), we generated transgenic mice expressing two human PS1 alleles: one with the aspartate to alanine mutation at residue 257 (hPS1D257A) that impairs the proteolytic activity of PS1, and the other deleting amino acids 340-371 of the hydrophilic loop sequence (hPS1Δcat) essential for β-catenin interaction. We show here that although hPS1Δcat is fully competent in rescuing the PS1-null lethal phenotype, hPS1D257A does not exhibit developmental activity. hPS1D257A also leads to the concurrent loss of the proteolytic processing of Notch and β-amyloid precursor protein (APP) and the generation of β-amyloid peptides (Aβ). Further, by measuring the levels of endogenous AβX-40 and AβX-42 in primary neuronal cultures, we confirmed the concept that PS1 is indispensable for the production of secreted Aβ.

Original languageEnglish (US)
Pages (from-to)8760-8765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number13
DOIs
StatePublished - Jun 25 2002
Externally publishedYes

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Presenilin-1
Catenins
Amyloid
Aspartic Acid
Peptides
Amyloid beta-Protein Precursor
Alanine
Transgenic Mice
Alleles
Phenotype
Amino Acids
Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms. / Xia, Xuefeng; Wang, Pei; Sun, Xiaoyan; Soriano, Salvador; Shum, Wan Kyng; Yamaguchi, Haruyasu; Trumbauer, Myrna E.; Takashima, Akihiko; Koo, Edward H.; Zheng, Hui.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 13, 25.06.2002, p. 8760-8765.

Research output: Contribution to journalArticle

Xia, Xuefeng ; Wang, Pei ; Sun, Xiaoyan ; Soriano, Salvador ; Shum, Wan Kyng ; Yamaguchi, Haruyasu ; Trumbauer, Myrna E. ; Takashima, Akihiko ; Koo, Edward H. ; Zheng, Hui. / The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 13. pp. 8760-8765.
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AU - Soriano, Salvador

AU - Shum, Wan Kyng

AU - Yamaguchi, Haruyasu

AU - Trumbauer, Myrna E.

AU - Takashima, Akihiko

AU - Koo, Edward H.

AU - Zheng, Hui

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