DOI: 10.1046/j.1471-4159.2002.01207.x. The levels of mature glycosylated nicastrin are regulated and correlate with γ‐secretase processing of amyloid β‐precursor protein

The levels of mature glycosylated nicastrin are regulated and correlate with γ‐secretase processing of amyloid β‐precursor protein

10.1046/j.1471-4159.2002.01207.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

AbstractNicastrin, a type‐I transmembrane glycoprotein, is a necessary component of the high molecular weight presenilin (PS) complexes that mediate intramembranous cleavage of β‐amyloid precursor protein (βAPP) and Notch. Nicastrin undergoes trafficking‐dependent glycosylation maturation, and PS1 interacts preferentially with these maturely glycosylated forms of nicastrin. We investigated the effects of differing levels of the immature and mature endoglycosidase‐H‐resistant forms of nicastrin on Aβ40‐ and Aβ42‐peptide secretion in several cell lines stably expressing a mutant nicastrin (D336A/Y337A) that increases Aβ secretion. There was no correlation between Aβ secretion and the level of over‐expression of the immature forms of nicastrin. The total level of mature nicastrin remained constant, but mutant nicastrin replaced endogenous mature nicastrin in varying degrees. Differences in the levels of mature mutant nicastrin positively correlated with Aβ secretion, but did not influence either βAPP trafficking or processing by α‐ and β‐secretases. Proper trafficking and terminal maturation of nicastrin is therefore a necessary event for the regulated intramembranous proteolysis of βAPP.

Bibliography

Arawaka, S., Hasegawa, H., Tandon, A., Janus, C., Chen, F., Yu, G., Kikuchi, K., Koyama, S., Kato, T., Fraser, P. E., & St GeorgeâHyslop, P. (2002). The levels of mature glycosylated nicastrin are regulated and correlate with Î³âsecretase processing of amyloid Î²âprecursor protein. Journal of Neurochemistry, 83(5), 1065â1071. Portico.

Authors 11

Shigeki Arawaka (first)
Hiroshi Hasegawa (additional)
Anurag Tandon (additional)
Christopher Janus (additional)
Fusheng Chen (additional)
Gang Yu (additional)
Kenji Kikuchi (additional)
Shingo Koyama (additional)
Takeo Kato (additional)
Paul E. Fraser (additional)
Peter St George‐Hyslop (additional)

References 18 Referenced 35

10.1001/jama.286.18.2257
10.1016/S0092-8674(00)80675-3
10.1074/jbc.M006986200
10.1038/35087069
10.1038/ncb1201-1129
10.1073/pnas.132277899
10.1016/S0925-4439(00)00028-4
{'key': 'e_1_2_12_9_1', 'volume-title': 'Statistical Methods for Psychology', 'author': 'Howell D. C.', 'year': '1992'} / Statistical Methods for Psychology by Howell D. C. (1992)
10.1016/S1534-5807(01)00105-8
10.1074/jbc.C200148200
10.1006/dbio.2001.0486
10.1016/S1534-5807(01)00109-5
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10.1038/376775a0
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10.1097/00001756-200009280-00035

Dates

Type	When
Created	22 years, 5 months ago (March 12, 2003, 2:03 a.m.)
Deposited	1 year, 11 months ago (Sept. 27, 2023, 4:15 p.m.)
Indexed	2 months, 1 week ago (June 27, 2025, 5:03 a.m.)
Issued	22 years, 9 months ago (Nov. 19, 2002)
Published	22 years, 9 months ago (Nov. 19, 2002)
Published Online	22 years, 9 months ago (Nov. 19, 2002)
Published Print	22 years, 9 months ago (Dec. 1, 2002)

Funders 0

None

BibTeX

@article{Arawaka_2002, title={The levels of mature glycosylated nicastrin are regulated and correlate with γ‐secretase processing of amyloid β‐precursor protein}, volume={83}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2002.01207.x}, DOI={10.1046/j.1471-4159.2002.01207.x}, number={5}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Arawaka, Shigeki and Hasegawa, Hiroshi and Tandon, Anurag and Janus, Christopher and Chen, Fusheng and Yu, Gang and Kikuchi, Kenji and Koyama, Shingo and Kato, Takeo and Fraser, Paul E. and St George‐Hyslop, Peter}, year={2002}, month=nov, pages={1065–1071} }

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