| First Author | Marjoram RJ | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 11 | Pages | e114035 |
| PubMed ID | 25415203 | Mgi Jnum | J:225288 |
| Mgi Id | MGI:5692352 | Doi | 10.1371/journal.pone.0114035 |
| Citation | Marjoram RJ, et al. (2014) alpha2beta1 integrin, GPVI receptor, and common FcRgamma chain on mouse platelets mediate distinct responses to collagen in models of thrombosis. PLoS One 9(11):e114035 |
| abstractText | OBJECTIVE: Platelets express the alpha2beta1 integrin and the glycoprotein VI (GPVI)/FcRgamma complex, both collagen receptors. Understanding platelet-collagen receptor function has been enhanced through use of genetically modified mouse models. Previous studies of GPVI/FcRgamma-mediated collagen-induced platelet activation were perfomed with mice in which the FcRgamma subunit was genetically deleted (FcRgamma-/-) or the complex was depleted. The development of alpha2beta1-/- and GPVI-/- mice permits side-by-side comparison to address contributions of these collagen receptors in vivo and in vitro. APPROACH AND RESULTS: To understand the different roles played by the alpha2beta1 integrin, the GPVI receptor or FcRgamma subunit in collagen-stimulated hemostasis and thrombosis, we compared alpha2beta1-/-, FcRgamma-/-, and GPVI-/- mice in models of endothelial injury and intravascular thrombosis in vivo and their platelets in collagen-stimulated activation in vitro. We demonstrate that both the alpha2beta1 integrin and the GPVI receptor, but not the FcRgamma subunit influence carotid artery occlusion in vivo. In contrast, the GPVI receptor and the FcRgamma chain, but not the alpha2beta1 integrin, play similar roles in intravascular thrombosis in response to soluble Type I collagen. FcRgamma-/- platelets showed less attenuation of tyrosine phosphorylation of several proteins including RhoGDI when compared to GPVI-/- and wild type platelets. The difference between FcRgamma-/- and GPVI-/- platelet phosphotyrosine levels correlated with the in vivo thrombosis findings. CONCLUSION: Our data demonstrate that genetic deletion of GPVI receptor, FcRgamma chain, or the alpha2beta1 integrin changes the thrombotic potentials of these platelets to collagen dependent on the stimulus mechanism. The data suggest that the FcRgamma chain may provide a dominant negative effect through modulating signaling pathways in platelets involving several tyrosine phosphorylated proteins such as RhoGDI. In addition, these findings suggest a more complex signaling network downstream of the platelet collagen receptors than previously appreciated. |
