<<< Full experiment listing

PXD000697

PXD000697 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAlterations in the Interactome of Serine/Threonine Protein Phosphatase Type-1 in Atrial Fibrillation Patients
DescriptionObjectives: To test the hypothesis that serine/threonine protein phosphatase type-1 (PP1) is dysregulated in paroxysmal atrial fibrillation (pAF) at the level of its regulatory subunits (R-subunits). Background: AF is the most common sustained cardiac arrhythmia yet current pharmacologic treatment is ineffective. PP1, a major phosphatase in the heart, consists of a catalytic subunit (PP1c) and a large set of R-subunits that confer localization and substrate specificity to the holoenzyme. Previous studies suggest that PP1 is dysregulated in AF but the mechanisms are unknown. Methods: Cardiac lysates were co-immunoprecipitated with anti-PP1c antibody followed by mass spectrometry-based (quantitative) profiling of associated R-subunits. Subsequently, label-free quantification was used to evaluate altered R-subunit-PP1c interactions in pAF patients. R-subunits with altered binding to PP1c in pAF were further validated using qRT-PCR, Western blotting (WB), immunocytochemistry, and co-immunoprecipitation. Results: 135 and 78 putative PP1c-interactors were captured respectively from mouse ventricles and human atria, with many previously unreported interactors with conserved PP1c-docking motifs. Increases in binding were found between PP1c and PPP1R7, CSDA, and PDE5A in pAF patients, with CSDA and PDE5A being novel interactors validated by bioinformatics, immunocytochemistry and co-immunoprecipitation. WB confirmed that these upregulated associations cannot be ascribed to changes in global protein expression alone. Conclusion: Subcellular heterogeneity in PP1 activity and downstream protein phosphorylation in AF may be attributed to alterations in PP1c-R-subunits interactions, which impair PP1 targeting to proteins involved in electrical and Ca2+-remodeling. This represents a novel concept in AF pathogenesis and provides highly-specific drug targets for treating AF.
HostingRepositoryPRIDE
AnnounceDate2015-03-31
AnnouncementXMLSubmission_2015-03-31_00:31:04.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNicolas Lebesgue
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive; LTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02014-01-21 03:22:40ID requested
12015-03-30 05:44:19announced
22015-03-31 00:31:06announcedUpdated project metadata.
Publication List
Keyword List
curator keyword: Biomedical
submitter keyword: protein phosphatase 1, paroxysmal atrial fibrillation, mouse, human, Q-exactive, LTQ-Orbitrap Elite, label-free quantification
Contact List
Arjen Scholten
contact affiliationBiomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University Padualaan 8 3584 CH Utrecht The Netherlands, Janssen Infectious Diseases and Vaccines, Crucell Holland B.V., Leiden, the Netherlands
contact emailA.Scholten@uu.nl
lab head
Nicolas Lebesgue
contact affiliationUtrecht University
contact emailn.f.m.lebesgue@uu.nl
dataset submitter
Full Dataset Link List
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/2015/03/PXD000697
PRIDE project URI
Repository Record List
[ + ]