<<< Full experiment listing

PXD031321

PXD031321 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCalpain Cleavage of Junctophilin-2 generates a Spectrum of Calcium-dependent Cleavage Products and DNA-rich NT1-Fragment Domains in Cardiomyocytes
DescriptionCalpains are calcium (Ca2+) activated neutral proteases that are involved in several essential signaling pathways. One Calpain-specific proteolytic target is Junctophilin-2 (JP2), an important structural protein of Ca2+ release units required for the excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in mouse models of heart failure has been reported previously, the precise molecular identity of the Calpain cleavage sites and the (patho-) physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565 but subsequently also at three additional secondary Calpain cleavage sites. We identified the Calpain-specific primary cleavage products not only in mouse but also in human iPSC-derived cardiomyocytes (hiPSC-CMs). Knockout of RyR2 in hiPSC-CMs destabilized JP2 resulting in an increase of the Calpain-specifc cleavage fragments. The primary N-terminal cleavage product (NT1) accumulated in the nucleus of mouse and human cardiomyocytes in a Ca2+ dependent manner, closely associated with DNA-rich chromosomal regions, where NT1 is proposed to function as a cardioprotective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies.
HostingRepositoryPRIDE
AnnounceDate2022-08-12
AnnouncementXMLSubmission_2022-08-12_00:25:57.558.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristof Lenz
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-30 10:48:06ID requested
12022-08-12 00:25:58announced
Publication List
Weninger G, Pochechueva T, El Chami D, Luo X, Kohl T, Brandenburg S, Urlaub H, Guan K, Lenz C, Lehnart SE, -fragment domains in cardiomyocytes. Sci Rep, 12(1):10387(2022) [pubmed]
Keyword List
submitter keyword: Calcium, Calpain, Cardiomyocyte, Junctophilin, Ryanodine
Contact List
Christof Lenz
contact affiliationCore Facility Proteomics, Department of Clinical Chemistry, University Medical Center Göttingen, Germany
contact emailchristof.lenz@med.uni-goettingen.de
lab head
Christof Lenz
contact affiliationMax Planck Institute for Biophysical Chemistry
contact emailchristof.lenz@mpibpc.mpg.de
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/2022/08/PXD031321
PRIDE project URI
Repository Record List
[ + ]