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Cited by 181

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Presenilin 1 Is Required for Maturation and Cell Surface Accumulation of Nicastrin

Open access
Leem, Jae Yoon, Vijayan, Shrijay, Han, Ping, Cai, Dongming, Machura, Michael, Lopes, Kryslaine O., Veselits, Margaret L., Xu, Huaxi, Thinakaran, Gopal·2002·Journal of Biological Chemistry

Abstract

Proteolytic processing of amyloid precursor protein generates beta-amyloid (Abeta) peptides that are deposited in senile plaques in brains of aged individuals and patients with Alzheimer's disease. Presenilins (PS1 and PS2) facilitate the final step in Abeta production, the intramembranous gamma-secretase cleavage of amyloid precursor protein. Biochemical and pharmacological evidence support a catalytic or accessory role for PS1 in gamma-secretase cleavage, as well as a regulatory role in select membrane protein trafficking. In this report, we demonstrate that PS1 is required for maturation and cell surface accumulation of nicastrin, an integral component of the multimeric gamma-secretase complex. Using kinetic labeling studies we show that in PS1(-/-)/PS2(-/-) cells nicastrin fails to reach the medial Golgi compartment, and as a consequence, is incompletely glycosylated. Stable expression of human PS1 restores these deficiencies in PS1(-/-) fibroblasts. Moreover, membrane fractionation studies show co-localization of PS1 fragments with mature nicastrin. These results indicate a novel chaperone-type role for PS1 and PS2 in facilitating nicastrin maturation and transport in the early biosynthetic compartments. Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex.

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Metadata

Authors
Leem, J. Y., Vijayan, S., Han, P., Cai, D., Machura, M., Lopes, K. O., Veselits, M. L., Xu, H., & Thinakaran, G.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-05
Volume
277
Issue
21
Pages
19236-19240
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1991549727
Cited by
181
References
5
FWCI
16.72
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Presenilin 1 Is Required for Maturation and Cell Surface Accumulation of Nicastrin. https://app.cochat.ai/papers/10.1074/jbc.c200148200
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Leem, J. Y., Vijayan, S., Han, P., Cai, D., Machura, M., Lopes, K. O., Veselits, M. L., Xu, H., & Thinakaran, G. (2002). Presenilin 1 Is Required for Maturation and Cell Surface Accumulation of Nicastrin. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c200148200

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