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Title: N-glycosylation of human nicastrin is required for interaction with the lectins from the secretory pathway calnexin and ERGIC-53
Authors: Morais, Vanessa
Brito, Catarina
Pijak, Donald S
Crystal, Adam S
Fortna, Ryan R
Li, Tong
Wong, Phil C
Doms, Robert W
Costa, Julia # ×
Issue Date: Sep-2006
Publisher: Elsevier
Series Title: Biochimica et Biophysica Acta. Molecular Basis of Disease vol:1762 issue:9 pages:802-810
Abstract: The gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin (NCT), APH-1 and PEN-2, is responsible for the intramembranous cleavage of amyloid precursor protein (APP), Notch and several other type 1 transmembrane proteins. gamma-Secretase cleavage of APP releases the A beta peptides, which form the amyloid plaques characteristic of Alzheimer's disease brains, and cleavage of Notch releases an intracellular signalling peptide that is critical for numerous developmental processes. NCT, a type I membrane protein, is the only protein within the complex that is glycosylated. The importance of these glycosylation sites is not fully understood. Here, we have observed that NCT N-linked oligosaccharides mediated specific interactions with the secretory pathway lectins calnexin and ERGIC-53. In order to investigate the role played by N-glycosylation, mutation of each site was performed. All hNCT mutants interacted with calnexin and ERGIC-53, indicating that the association was not mediated by any single Ar-glycosylation site. Moreover, the interaction with ERGIC-53 still occurred in PS1/2 double knockout cells as detected in immunoprecipitation as well as confocal immuno fluorescence microscopy studies, which indicated that NCT interacted with ERGIC-53 prior to its association with the active gamma-secretase complex. (c) 2006 Elsevier B.V. All rights reserved.
URI: 
ISSN: 0925-4439
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for the Research of Neurodegenerative Diseases
× corresponding author
# (joint) last author

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