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Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              By studying a mouse model (cKO [conditional knockout]\n              <jats:sup>Kif5b<\/jats:sup>\n              ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model. This instability was confirmed in vitro in a whole-blood perfusion assay under blood flow conditions. Aggregations induced by thrombin and collagen were also impaired in cKO\n              <jats:sup>Kif5b<\/jats:sup>\n              platelets. Furthermore, P-selectin exposure, PF4 (platelet factor 4) secretion, and ATP release after thrombin stimulation were impaired in cKO\n              <jats:sup>Kif5b<\/jats:sup>\n              platelets, highlighting the role of kinesin-1 in \u03b1-granule and dense granule secretion. Importantly, exogenous ADP rescued normal thrombin induced-aggregation in cKO\n              <jats:sup>Kif5b<\/jats:sup>\n              platelets, which indicates that impaired aggregation was because of defective release of ADP and dense granules. Last, we demonstrated that kinesin-1 interacts with the molecular machinery comprising the granule-associated Rab27 (Ras-related protein Rab-27) protein and the Slp4 (synaptotagmin-like protein 4\/SYTL4) adaptor protein.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our results indicate that a kinesin-1\u2013dependent process plays a role for platelet function by acting into the mechanism underlying \u03b1-granule and dense granule secretion.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310373","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T10:00:10Z","timestamp":1520503210000},"page":"1037-1051","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Kinesin-1 Is a New Actor Involved in Platelet Secretion and Thrombus 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