title: Proplatelet formation is selectively inhibited by collagen type I through Syk-independent GPVI signaling.
abstract: 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.
authors: Institute of Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, Germany.
authors: Daniela
authors: D
authors: Semeniak
authors: Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany.
authors: Rebecca
authors: R
authors: Kulawig
authors: Institute of Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, Germany Rudolf Virchow-Zentrum, University of Würzburg, 97080 Würzburg, Germany.
authors: David
authors: D
authors: Stegner
authors: Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany.
authors: Imke
authors: I
authors: Meyer
authors: Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany.
authors: Silke
authors: S
authors: Schwiebert
authors: Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany.
authors: Hendrik
authors: H
authors: Bösing
authors: Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
authors: Beate
authors: B
authors: Eckes
authors: Institute of Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, Germany Rudolf Virchow-Zentrum, University of Würzburg, 97080 Würzburg, Germany.
authors: Bernhard
authors: B
authors: Nieswandt
authors: Institute of Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, Germany Laboratory for Pediatric Molecular Biology, Charité-University Medicine, 13353 Berlin, Germany harald.schulze@uni-wuerzburg.de.
authors: Harald
authors: 0000-0003-1285-6407
authors: H
authors: Schulze
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D038981:Receptors, Collagen / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D000072377:Syk Kinase; C000606897:Syk protein, mouse
keywords: Collagen; Collagen receptor; Proplatelet formation; Thrombopoiesis