PXD001942

PXD001942 is an original dataset announced via ProteomeXchange.

Title	Quantitative interaction proteomics of neurodegenerative disease proteins
Description	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-2 (PARK-2) for Parkinson’s disease and Ataxin-1 (ATXN-1) 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.
HostingRepository	PRIDE
AnnounceDate	2015-09-22
AnnouncementXML	Submission_2015-09-22_05:57:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-16 09:37:16	ID requested
⏵ 1	2015-09-22 05:57:39	announced

Hosp F, Vossfeldt H, Heinig M, Vasiljevic D, Arumughan A, Wyler E, Landthaler M, Hubner N, Wanker EE, Lannfelt L, Ingelsson M, Lalowski M, Voigt A, Selbach M, Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Chapman J, Russo G, Hamshere M, Pahwa JS, Escott-Price V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan A, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown K, Passmore P, Craig D, McGuinness B, Todd S, Johnston J, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Heun R, Sch, ü, rmann B, Ramirez A, Becker T, Herold C, Lacour A, Drichel D, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Fr, ö, lich L, Hampel H, H, ü, ll M, Rujescu D, Goate A, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Singleton AB, Guerreiro R, M, ü, hleisen TW, N, ö, then MM, Moebus S, J, ö, ckel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans P, O'Donovan M, J Owen M, Williams J, Quantitative interaction proteomics of neurodegenerative disease proteins. Cell Rep, 11(7):1134-46(2015) [pubmed]

submitter keyword: qAP-MS, neurodegeneration

Matthias Selbach
contact affiliation	Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.13, 13092 Berlin, Germany
contact email	matthias.selbach@mdc-berlin.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2015/09/PXD001942

PRIDE project URI

• PRIDE
  1. PXD001942
     1. Label: PRIDE project
     2. Name: Quantitative interaction proteomics of neurodegenerative disease proteins