Thromb Haemost 2024; 124(02): 122-134
DOI: 10.1055/a-2166-5841
Cellular Haemostasis and Platelets

The C-Type Lectin Receptor CD93 Regulates Platelet Activation and Surface Expression of the Protease Activated Receptor 4

Silvia Maria Grazia Trivigno
1   University School for Advanced Studies IUSS, Pavia, Italy
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
Mauro Vismara
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
3   Department of Molecular Medicine, University of Pavia, Pavia, Italy
Ilaria Canobbio
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
Serena Rustichelli
1   University School for Advanced Studies IUSS, Pavia, Italy
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
Federico Galvagni
4   Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
Maurizio Orlandini
4   Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
Mauro Torti
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
Gianni Francesco Guidetti
2   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
› Author Affiliations
Funding This research was supported by the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018–2022)—Dept. of Biology and Biotechnology “L. Spallanzani,” University of Pavia.


Background The C-type lectin receptor CD93 is a single pass type I transmembrane glycoprotein involved in inflammation, immunity, and angiogenesis. This study investigates the role of CD93 in platelet function. CD93 knockout (KO) mice and wild-type (WT) controls were compared in this study.

Methods Platelet activation and aggregation were investigated by flow cytometry and light transmission aggregometry, respectively. Protein expression and phosphorylation were analyzed by immunoblotting. Subcellular localization of membrane receptors was investigated by wide-field and confocal microscopy.

Results The lack of CD93 in mice was not associated to any evident bleeding defect and no alterations of platelet activation were observed upon stimulation with thromboxane A2 analogue and convulxin. Conversely, platelet aggregation induced by stimulation of the thrombin receptor PAR4 was significantly reduced in the absence of CD93. This defect was associated with a significant reduction of α-granule secretion, integrin αIIbβ3 activation, and protein kinase C (PKC) stimulation. Resting WT and CD93-deficient platelets expressed comparable amounts of PAR4. However, upon stimulation with a PAR4 activating peptide, a more pronounced clearance of PAR4 from the platelet surface was observed in CD93-deficient platelets compared with WT controls. Confocal microscopy analysis revealed a massive movement of PAR4 in cytosolic compartments of activated platelets lacking CD93. Accordingly, platelet desensitization following PAR4 stimulation was more pronounced in CD93 KO platelets compared with WT controls.

Conclusion These results demonstrate that CD93 supports platelet activation triggered by PAR4 stimulation and is required to stabilize the expression of the thrombin receptor on the cell surface.

Authors' Contribution

S.M.G.T., M.V., S.R., I.C.: performed the experiments, analyzed the data, and edited the manuscript; F.G., M.O.: provided vital reagents, discussed the results, and edited the manuscript; M.T., G.F.G.: designed the study, analyzed and interpreted the data, and drafted the manuscript.

Supplementary Material

Publication History

Received: 18 April 2023

Accepted: 04 September 2023

Accepted Manuscript online:
05 September 2023

Article published online:
30 September 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

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