Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Oct;11(1):64-82.
doi: 10.1006/nbdi.2002.0546.

A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface

Jae Yoon Leem  1 , Carlos A Saura, Claus Pietrzik, John Christianson, Christian Wanamaker, LaShaunda T King, Margaret L Veselits, Taisuke Tomita, Laura Gasparini, Takeshi Iwatsubo, Huaxi Xu, William N Green, Edward H Koo, Gopal Thinakaran
Affiliations

A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface

Jae Yoon Leem et al. Neurobiol Dis. 2002 Oct.

Abstract

Presenilin 1 (PS1) and presenilin 2 play a critical role in the gamma-secretase processing of amyloid precursor protein (APP) and Notch1. Here, we investigate maturation and intracellular trafficking of APP and other membrane proteins in cells expressing an experimental PS1 deletion mutant (deltaM1,2). Stable expression of deltaM1,2 impairs gamma-secretase processing of Notch1 and delays Abeta secretion. Kinetic studies show enhanced O-glycosylation and sialylation of holo-APP and marked accumulation of APP COOH-terminal fragments (CTFs). Surface biotinylation, live staining, and trafficking studies show increased surface accumulation of holo-APP and CTFs in deltaM1,2 cells resulting from enhanced surface delivery of newly synthesized APP. Expression of a loss-of-function PS1 mutant (D385A) or incubation of cells with gamma-secretase inhibitors also increases surface levels of holo-APP and CTFs. In contrast to APP, glycosylation and surface accumulation of another type I membrane protein, nicastrin, are markedly reduced in deltaM1,2 cells. Finally, expression of deltaM1,2 results in the increased assembly and surface expression of nicotinic acetylcholine receptors, illustrating that PS1's influence on protein trafficking extends beyond APP and other type I membrane protein substrates of gamma-secretase. Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources