DOI: 10.1073/pnas.132045399. The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms

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

10.1073/pnas.132045399

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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 Aβ X-40 and Aβ X-42 in primary neuronal cultures, we confirmed the concept that PS1 is indispensable for the production of secreted Aβ.

Bibliography

Xia, X., Wang, P., Sun, X., Soriano, S., Shum, W.-K., Yamaguchi, H., Trumbauer, M. E., Takashima, A., Koo, E. H., & Zheng, H. (2002). The aspartate-257 of presenilin 1 is indispensable for mouse development and production of Î²-amyloid peptides through Î²-catenin-independent mechanisms. Proceedings of the National Academy of Sciences, 99(13), 8760â8765.

Authors 10

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

References 37 Referenced 26

Dates

Type	When
Created	23 years ago (July 28, 2002, 6:26 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 11:16 p.m.)
Indexed	1 year, 2 months ago (June 17, 2024, 3:09 p.m.)
Issued	23 years, 2 months ago (June 17, 2002)
Published	23 years, 2 months ago (June 17, 2002)
Published Online	23 years, 2 months ago (June 17, 2002)
Published Print	23 years, 2 months ago (June 25, 2002)

Funders 0

None

BibTeX

@article{Xia_2002, title={The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.132045399}, DOI={10.1073/pnas.132045399}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Xia, Xuefeng and Wang, Pei and Sun, Xiaoyan and Soriano, Salvador and Shum, Wan-Kyng and Yamaguchi, Haruyasu and Trumbauer, Myrna E. and Takashima, Akihiko and Koo, Edward H. and Zheng, Hui}, year={2002}, month=jun, pages={8760–8765} }

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