English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

Hosp, F., Vossfeldt, H., Heinig, M., Vasiljevic, D., Arumughan, A., Wyler, E., et al. (2015). Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins. CELL REPORTS, 11(7), 1134-1146. doi:10.1016/j.celrep.2015.04.030.

Item is

Files

show Files
hide Files
:
1-s2.0-S2211124715004313-main.pdf (Any fulltext), 35MB
Name:
1-s2.0-S2211124715004313-main.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
open access article
License:
-

Locators

show

Creators

show
hide
 Creators:
Hosp, Fabian1, Author              
Vossfeldt, Hannes2, Author
Heinig, Matthias2, Author
Vasiljevic, Djordje2, Author
Arumughan, Anup2, Author
Wyler, Emanuel2, Author
Landthaler, Markus2, Author
Hubner, Norbert2, Author
Wanker, Erich E.2, Author
Lannfelt, Lars2, Author
Ingelsson, Martin2, Author
Lalowski, Maciej2, Author
Voigt, Aaron2, Author
Selbach, Matthias2, Author
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

Content

show
hide
Free keywords: AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; INTERACTION NETWORK; CELL-DEATH; MITOCHONDRIAL; ATAXIN-1; COMPLEX; EXPRESSION
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CELL REPORTS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 11 (7) Sequence Number: - Start / End Page: 1134 - 1146 Identifier: ISSN: 2211-1247