Miller, Bruce L

Publication Detail

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

Anja-Silke Beyer; Bjoern von Einem; Daniel Schwanzar; Ilona E Keller; Anke Hellrung; Dietmar R Thal; Martin Ingelsson; Alexandra Makarova; Meihua Deng; Ekta S Chhabra; et al. (Profiled Author: Hyman, Bradley T)

Department of Neurology, Center for Clinical Research, Ulm University, Helmholtzstrasse 8/1, D-89081 Ulm, Germany.
Neurobiology of aging 2012;33(4):732-43.

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.

4 Originating Grant

• 1.

  HYMAN, BRADLEY T

  Massachusetts Alzheimer's Disease Research Center

  1 April 1997 - 31 March 2014

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 13,238,070

• 2.

  Growdon, John H

  Massachusetts Alzheimer's Disease Research Center

  1 April 1997 - 31 March 2009

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 36,612,653

• 3.

  Hyman, Bradley T

  LRP AND ALZHEIMER'S DISEASE

  1 September 1994 - 31 January 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 4,716,276

• 4.

  Hyman, Bradley T

  APOLIPOPROTEIN E AND ALZHEIMERS DISEASE

  Total Funding: $ 1,232,570

Scientific Context

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