First Author | Wersäll A | Year | 2018 |
Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
Issue | 4 | Pages | 787-800 |
PubMed ID | 29437579 | Mgi Jnum | J:274625 |
Mgi Id | MGI:6296351 | Doi | 10.1161/ATVBAHA.117.310294 |
Citation | Wersall A, et al. (2018) Mouse Platelet Ral GTPases Control P-Selectin Surface Expression, Regulating Platelet-Leukocyte Interaction. Arterioscler Thromb Vasc Biol 38(4):787-800 |
abstractText | OBJECTIVE: RalA and RalB GTPases are important regulators of cell growth, cancer metastasis, and granule secretion. The purpose of this study was to determine the role of Ral GTPases in platelets with the use of platelet-specific gene-knockout mouse models. APPROACH AND RESULTS: This study shows that platelets from double knockout mice, in which both GTPases have been deleted, show markedly diminished ( approximately 85% reduction) P-selectin translocation to the surface membrane, suggesting a critical role in alpha-granule secretion. Surprisingly, however, there were only minor effects on stimulated release of soluble alpha- and delta-granule content, with no alteration in granule count, morphology, or content. In addition, their expression was not essential for platelet aggregation or thrombus formation. However, absence of surface P-selectin caused a marked reduction ( approximately 70%) in platelet-leukocyte interactions in blood from RalAB double knockout mice, suggesting a role for platelet Rals in platelet-mediated inflammation. CONCLUSIONS: Platelet Ral GTPases primarily control P-selectin surface expression, in turn regulating platelet-leukocyte interaction. Ral GTPases could therefore be important novel targets for the selective control of platelet-mediated immune cell recruitment and inflammatory disease. |