Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurobiol Aging. 2012 Apr;33(4):732-43. doi: 10.1016/j.neurobiolaging.2010.06.006. Epub 2010 Jul 31.

Engulfment adapter PTB domain containing 1 interacts with and affects processing of the amyloid-β precursor protein.

Author information

  • 1Department of Neurology, Center for Clinical Research, Ulm University, Helmholtzstrasse 8/1, D-89081 Ulm, Germany.

Abstract

Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-β A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of Aβ40/42 and sAPPα. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
20674096
[PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk