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PXD021271-1

PXD021271 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCyclin Y is expressed in platelets and modulates integrin outside-in signaling
DescriptionDiabetes is associated with platelet hyperactivation and enhanced risk of thrombosis development. We have previously shown that calpain inhibition stabilizes the platelet proteome in diabetic patients. However, a global proteome analysis comparing platelets from healthy donors and from diabetic patients is missing. Therefore, we performed comparative proteomic studies to identify differentially expressed proteins and their possible function in platelet activation. Mass spectrometry analysis identified cyclin Y in platelets and levels were found to be reduced in platelets from diabetic patients. In the latter, cyclin Y was degraded by the protease calpain. In order to assess the function of cylcin Y in platelets, mice globally lacking cyclin Y were generated using CRISPR/Cas9 technology by inserting a premature Stop codon in exon 1 of Ccny gene. Cyclin Y deletion resulted in a reduction in the circulating platelet number but the agonist-induced platelet aggregation was comparable in platelets from wild-type and Ccny-/- mice, as was agonist-induced α and dense granule secretion. However, cyclin Y-deficient platelets demonstrated enhanced adhesion to fibronectin and collagen as well as an attenuated spreading and clot retraction, indicating an alteration in “outside in” integrin signalling. The phenotype was accompanied by a significant reduction in the agonist-induced tyrosine phosphorylation of the β3 integrin in Ccny-/- platelets. Stimulation of human platelets or platelets from wildtype mice with thrombin led to the membrane translocation of cyclin Y where it associates with the tyrosine kinase Fyn suggesting that cyclin Y might play a role as an adaptor protein for the tyrosine kinase to phosphorylate the cytoplasmic tail of the β3 integrin. Thus, cyclin Y is present in anucleated platelets where it is involved in the regulation of integrin-mediated outside in signalling.
HostingRepositoryPRIDE
AnnounceDate2024-10-07
AnnouncementXMLSubmission_2024-10-07_10:44:44.396.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD021271
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterFiorella Andrea Solari
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-02 07:13:49ID requested
12024-10-07 10:44:44announced
Publication List
10.6019/PXD021271;
Keyword List
submitter keyword: proteomics,platelets, diabetes
Contact List
Albert Sickmann
contact affiliationLeibniz-Institut für Analytische Wissenschaften - ISAS - e.V.
contact emailalbert.sickmann@isas.de
lab head
Fiorella Andrea Solari
contact affiliationLeibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact emailfiorella.solari@isas.de
dataset submitter
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