Development of ligands for the platelet receptor CLEC-2

Abstract

Platelets are anucleate cells derived from megakaryocytes, which play an important role in the regulation of haemostasis and thrombosis at the injury site; however, they are also involved in other physiological processes such as inflammation, during which they interact with other immune cells including leukocytes. However, certain chronic inflammatory diseases may lead to an aberrant prothrombotic response, known as thromboinflammation. This process is modulated by certain platelet immune receptors, including CLEC-2, a C-type lectin-like type II transmembrane receptor. In this study we searched for novel ligands for the platelet receptor CLEC-2. We identified a new platelet agonist, called Katacine, which induces strong platelet aggregation through CLEC-2. We also developed multimeric nanobodies against this receptor and we suggested that tetrameric structures are needed to induce platelet aggregation, while lower order of oligomerisation are unable to induce platelet aggregation. But able to prevent platelet aggregation. The novel tools will facilitate further research on CLEC-2 function and the mode of activation of CLEC-2.