Glycoprotein V : the unsolved GPV puzzle

Abstract

Glycoprotein V (GPV) is a highly expressed 82 KDa platelet surface transmembrane protein which is loosely attached to the GPIb-IX complex. Despite remaining questions concerning its function, GPV presents several unique features which have repercussions in hematology, atherothrombosis, immunology and transfusion. GPV is specifically expressed in platelets and megakaryocytes and is an ideal marker and reporter gene for the late stages of megakaryopoiesis. The ectodomain of GPV can be released by a number of proteases, namely thrombin, elastase and ADAM10 and 17. Although it was originally proposed as a thrombin receptor, this hypothesis was abandoned since thrombin activation was preserved after blockade of GPV cleavage and in Gp5 knockout mice. The combined potential of GPV to reflect the direct action of thrombin, platelet exposure to strong agonists and inflammatory conditions has led one to evaluate its utility as a marker in the context of atherothrombosis. Increased plasma levels of soluble GPV have notably been recorded in myocardial infarction, stroke and venous thromboembolism. It is also highly valued in transfusion to monitor platelet storage lesions. GPV presents several polymorphisms, which are a possible source of alloantibodies, while autoantibodies have been frequently detected in immune thrombocytopenia. The real biological function of this glycoprotein nevertheless remains an enigma, despite the respectively decreased and increased responses to low concentrations of collagen and thrombin observed in Gp5 knockout mice. Current studies are exploring its role in modulating general or VWF-induced platelet signaling, which could bear relevance in thrombosis and platelet clearance.

Keywords:

• Glycoprotein V
• GPIb-IX complex
• platelets
• thrombosis

Acknowledgements

The authors would like to thank David Azorsa, Boris Aleil, Christelle Nonne, Adeline Lepage, Corinne de la Salle and Martine Santer for their essential contributions to the work summarized in this review; the numerous clinicians who participated in studies of GPV as a marker of thrombosis; David Phillips, Jean-Pierre Cazenave, Christian Gachet and Georges Uzan for their support at different stages of our work on GPV; Mark Kahn and Shaun Coughlin for providing the GPV KO strain and Juliette Mulvihill for reviewing the English of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

QK was supported by a grant from the Fondation pour la Recherche Médicale [FDT202106013085]. FL was the recipient of a Contrat d’interface between the Hôpitaux Universitaires de Strasbourg and INSERM.