PXD021271

PXD021271 is an original dataset announced via ProteomeXchange.

Title	Cyclin Y is expressed in platelets and modulates integrin outside-in signaling
Description	Diabetes 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:44:44.396.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021271
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fiorella Andrea Solari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-02 07:13:49	ID requested
⏵ 1	2024-10-07 10:44:44	announced

10.6019/PXD021271;

submitter keyword: proteomics,platelets, diabetes

Albert Sickmann
contact affiliation	Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V.
contact email	albert.sickmann@isas.de
lab head
Fiorella Andrea Solari
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact email	fiorella.solari@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021271
     1. Label: PRIDE project
     2. Name: Cyclin Y is expressed in platelets and modulates integrin outside-in signaling