TY  - JOUR
A1  - Kyselova, Anastasia
A1  - Siragusa, Mauro
A1  - Anthes, Julian
A1  - Solari, Fiorella Andrea
A1  - Loroch, Stefan
A1  - Zahedi, Rene P.
A1  - Walter, Ulrich
A1  - Fleming, Ingrid
A1  - Randriamboavonjy, Voahanginirina
T1  - Cyclin Y is expressed in platelets and modulates integrin outside-in signaling
T2  - International journal of molecular sciences
N2  - Diabetes is associated with platelet hyper-reactivity and enhanced risk of thrombosis development. Here we compared protein expression in platelets from healthy donors and diabetic patients to identify differentially expressed proteins and their possible function in platelet activation. Mass spectrometry analyses identified cyclin Y (CCNY) in platelets and its reduced expression in platelets from diabetic patients, a phenomenon that could be attributed to the increased activity of calpains. To determine the role of CCNY in platelets, mice globally lacking the protein were studied. CCNY-/- mice demonstrated lower numbers of circulating platelets but platelet responsiveness to thrombin and a thromboxane A2 analogue were comparable with that of wild-type mice, as was agonist-induced α and dense granule secretion. CCNY-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. This phenotype was accompanied by a significant reduction in the agonist-induced tyrosine phosphorylation of β3 integrin. Taken together we have shown that CCNY is present in anucleated platelets where it is involved in the regulation of integrin-mediated outside in signalling associated with thrombin stimulation.
KW  - cyclin Y
KW  - integrin
KW  - outside-in signaling
KW  - spreading
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61978
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-619784
SN  - 1422-0067
VL  - 21
IS  - 21, art. 8239
SP  - 1
EP  - 13
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -