Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

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Hosp , F , Vossfeldt , H , Heinig , M , Vasiljevic , D , Arumughan , A , Wyler , E , Landthaler , M , Hubner , N , Wanker , E E , Lannfelt , L , Ingelsson , M , Lalowski , M , Voigt , A , Selbach , M & Genetic & Environm Risk Alzheimer' 2015 , ' Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins ' Cell Reports , vol. 11 , no. 7 , pp. 1134-1146 . DOI: 10.1016/j.celrep.2015.04.030

Title: Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins
Author: Hosp, Fabian; Vossfeldt, Hannes; Heinig, Matthias; Vasiljevic, Djordje; Arumughan, Anup; Wyler, Emanuel; Landthaler, Markus; Hubner, Norbert; Wanker, Erich E.; Lannfelt, Lars; Ingelsson, Martin; Lalowski, Maciej; Voigt, Aaron; Selbach, Matthias; Genetic & Environm Risk Alzheimer'
Contributor: University of Helsinki, Department of Biochemistry and Developmental Biology
Date: 2015-05-19
Language: eng
Number of pages: 13
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/165443
Abstract: Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.
Subject: AMYLOID PRECURSOR PROTEIN
GENOME-WIDE ASSOCIATION
ALZHEIMERS-DISEASE
MASS-SPECTROMETRY
INTERACTION NETWORK
CELL-DEATH
MITOCHONDRIAL
ATAXIN-1
COMPLEX
EXPRESSION
3111 Biomedicine
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