Semeniak Daniela, Kulawig Rebecca, Stegner David, Meyer Imke, Schwiebert Silke, Bösing Hendrik, Eckes Beate, Nieswandt Bernhard, Schulze Harald
Institute of Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, Germany.
Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany.
J Cell Sci. 2016 Sep 15;129(18):3473-84. doi: 10.1242/jcs.187971. Epub 2016 Aug 5.
Collagen receptors GPVI (also known as GP6) and integrin α2β1 are highly expressed on blood platelets and megakaryocytes, their immediate precursors. After vessel injury, subendothelial collagen becomes exposed and induces platelet activation to prevent blood loss. Collagen types I and IV are thought to have opposite effects on platelet biogenesis, directing proplatelet formation (PPF) towards the blood vessels to prevent premature release within the marrow cavity. We used megakaryocytes lacking collagen receptors or treated megakaryocytes with blocking antibodies, and could demonstrate that collagen-I-mediated inhibition of PPF is specifically controlled by GPVI. Other collagen types competed for binding and diminished the inhibitory signal, which was entirely dependent on receptor-proximal Src family kinases, whereas Syk and LAT were dispensable. Adhesion assays indicate that megakaryocyte binding to collagens is mediated by α2β1, and that collagen IV at the vascular niche might displace collagen I from megakaryocytes and thus contribute to prevention of premature platelet release into the marrow cavity and thereby directionally promote PPF at the vasculature.
胶原蛋白受体糖蛋白VI（也称为GP6）和整合素α2β1在血小板和巨核细胞（它们的直接前体细胞）上高度表达。血管损伤后，内皮下胶原蛋白暴露，诱导血小板活化以防止失血。I型和IV型胶原蛋白被认为对血小板生成具有相反的作用，引导前血小板形成（PPF）朝向血管，以防止在骨髓腔内过早释放。我们使用缺乏胶原蛋白受体的巨核细胞或用阻断抗体处理巨核细胞，并能够证明I型胶原蛋白介导的PPF抑制是由GPVI特异性控制的。其他类型的胶原蛋白竞争结合并减弱抑制信号，这完全依赖于受体近端的Src家族激酶，而Syk和LAT则是可有可无的。粘附试验表明，巨核细胞与胶原蛋白的结合是由α2β1介导的，血管龛处的IV型胶原蛋白可能会将I型胶原蛋白从巨核细胞中置换出来，从而有助于防止血小板过早释放到骨髓腔中，从而在脉管系统系统中定向促进PPF。
