Novel Mediators of Amyloid Precursor Protein Signaling

Andrzej Swistowski; Qiang Zhang; Mark E Orcholski; Danielle Crippen; Cathy Vitelli; Alexei Kurakin; Dale E Bredesen

doi:10.1523/JNEUROSCI.4351-09.2009

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Novel Mediators of Amyloid Precursor Protein Signaling

Journal article

Open access

Peer reviewed

Novel Mediators of Amyloid Precursor Protein Signaling

Andrzej Swistowski, Qiang Zhang, Mark E Orcholski, Danielle Crippen, Cathy Vitelli, Alexei Kurakin and Dale E Bredesen

The Journal of neuroscience, Vol.29(50), pp.15703-15712

12/16/2009

DOI: 10.1523/JNEUROSCI.4351-09.2009

PMCID: PMC2823633

PMID: 20016085

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Abstract

Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but the APP-dependent signaling network involved has not been defined. Here, we report a novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of the APP-interacting proteins Mint1, Mint2, and Mint3 (X11α, X11β, and X11γ), and multiple novel interactors for these proteins, with the finding that transcriptional coactivators are highly represented among these interactors. Furthermore, we show that Mint3 interaction with a set of the transcriptional coactivators leads to nuclear localization and transactivation, whereas interaction of the same set with Mint1 or Mint2 prevents nuclear localization and transactivation. These results define new mediators of the signal transduction network mediated by APP.

Details

Title: Subtitle: Novel Mediators of Amyloid Precursor Protein Signaling
Creators: Andrzej Swistowski - Buck Institute for Age Research, Novato, California 94945, and
Qiang Zhang - Buck Institute for Age Research, Novato, California 94945, and
Mark E Orcholski - Buck Institute for Age Research, Novato, California 94945, and
Danielle Crippen - Buck Institute for Age Research, Novato, California 94945, and
Cathy Vitelli - Buck Institute for Age Research, Novato, California 94945, and
Alexei Kurakin - Buck Institute for Age Research, Novato, California 94945, and
Dale E Bredesen - Buck Institute for Age Research, Novato, California 94945, and
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(50), pp.15703-15712
Publisher: Society for Neuroscience
DOI: 10.1523/JNEUROSCI.4351-09.2009
PMID: 20016085
PMCID: PMC2823633
ISSN: 0270-6474
eISSN: 1529-2401
Language: English
Date published: 12/16/2009
Academic Unit: Neurology
Record Identifier: 9984013113302771

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