Mutation of potential N-linked glycosylation sites in the Alzheimer's disease amyloid precursor protein (APP).

Abstract:

:In order to study the mechanism of intracellular sorting and processing of the Alzheimer's disease amyloid precursor protein (APP), we deleted two potential N-linked glycosylation sites of APP by site-directed mutagenesis. Substitution of alanines for the critical asparagine residues Asn467 and Asn496 was performed. Wild-type and mutant APPs were expressed in COS-1 cells by cDNA transfection and the expressed of the protein and secretion of N-terminal large fragment was observed. The initial secretion of the mutant APP appeared to be slow compared with wild-type. In addition, we found that a distinct APP fragment, the cytosolic form, is transiently increased in the cytosol fraction of COS-1 cells. These results suggest that aberrant processing occurs following the expression of a mutant APP with Ala substituted for Asn, and that glycosylation may modulate the intracellular sorting of APP.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Yazaki M,Tagawa K,Maruyama K,Sorimachi H,Tsuchiya T,Ishiura S,Suzuki K

doi

10.1016/s0304-3940(96)13285-7

subject

Has Abstract

pub_date

1996-12-27 00:00:00

pages

57-60

issue

1

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(96)13285-7

journal_volume

221

pub_type

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