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.
The authors declare no competing or financial interests.
D. Semeniak, R.K. and I.M. performed experiments and analyzed data. D. Stegner, B.E. and B.N. provided essential reagents and analyzed data. S.S. and H.B. performed experiments. H.S. performed experiments, analyzed data and wrote the manuscript. He is fully responsible for this manuscript.
This study was supported by the Deutsche Forschungsgemeinschaft [grant numbers SCHU 1421/5-2 and SFB688-TPA21].
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.187971.supplemental
- Received March 1, 2016.
- Accepted July 28, 2016.
- © 2016. Published by The Company of Biologists Ltd