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Article: Kinesin-1 Is a New Actor Involved in Platelet Secretion and Thrombus Stability

TitleKinesin-1 Is a New Actor Involved in Platelet Secretion and Thrombus Stability
Authors
KeywordsBlood platelets
Hemostasis
Kinesin
Platelet secretion
Issue Date2018
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642
Citation
Arteriosclerosis, Thrombosis, and Vascular Biology, 2018, v. 38 n. 5, p. 1037-1051 How to Cite?
AbstractOBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. 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. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b) 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 cKOKif5b platelets. Furthermore, P-selectin exposure, PF4 (platelet factor 4) secretion, and ATP release after thrombin stimulation were impaired in cKOKif5b platelets, highlighting the role of kinesin-1 in α-granule and dense granule secretion. Importantly, exogenous ADP rescued normal thrombin induced-aggregation in cKOKif5b 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. CONCLUSIONS: Our results indicate that a kinesin-1-dependent process plays a role for platelet function by acting into the mechanism underlying α-granule and dense granule secretion. © 2018 American Heart Association, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/263873
ISSN
2023 Impact Factor: 7.4
2023 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFrédéric, A-
dc.contributor.authorAlexandre, K-
dc.contributor.authorMathieu, K-
dc.contributor.authorNicolas, G-
dc.contributor.authorIsabelle, M-
dc.contributor.authorBordet, JC-
dc.contributor.authorHuang, J-
dc.contributor.authorAlain, FC-
dc.contributor.authorDelphine, BG-
dc.contributor.authorGeneviève, SB-
dc.contributor.authorOlivier, CT-
dc.contributor.authorGaël, MA-
dc.date.accessioned2018-10-22T07:45:49Z-
dc.date.available2018-10-22T07:45:49Z-
dc.date.issued2018-
dc.identifier.citationArteriosclerosis, Thrombosis, and Vascular Biology, 2018, v. 38 n. 5, p. 1037-1051-
dc.identifier.issn1079-5642-
dc.identifier.urihttp://hdl.handle.net/10722/263873-
dc.description.abstractOBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. 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. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b) 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 cKOKif5b platelets. Furthermore, P-selectin exposure, PF4 (platelet factor 4) secretion, and ATP release after thrombin stimulation were impaired in cKOKif5b platelets, highlighting the role of kinesin-1 in α-granule and dense granule secretion. Importantly, exogenous ADP rescued normal thrombin induced-aggregation in cKOKif5b 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. CONCLUSIONS: Our results indicate that a kinesin-1-dependent process plays a role for platelet function by acting into the mechanism underlying α-granule and dense granule secretion. © 2018 American Heart Association, Inc.-
dc.languageeng-
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642-
dc.relation.ispartofArteriosclerosis, Thrombosis, and Vascular Biology-
dc.rightsThis is a non-final version of an article published in final form in Arteriosclerosis, Thrombosis, and Vascular Biology, 2018, v. 38 n. 5, p. 1037-1051-
dc.subjectBlood platelets-
dc.subjectHemostasis-
dc.subjectKinesin-
dc.subjectPlatelet secretion-
dc.titleKinesin-1 Is a New Actor Involved in Platelet Secretion and Thrombus Stability-
dc.typeArticle-
dc.identifier.emailHuang, J: jdhuang@hku.hk-
dc.identifier.authorityHuang, J=rp00451-
dc.description.naturepostprint-
dc.identifier.doi10.1161/ATVBAHA.117.310373-
dc.identifier.scopuseid_2-s2.0-85061763453-
dc.identifier.hkuros293621-
dc.identifier.volume38-
dc.identifier.issue5-
dc.identifier.spage1037-
dc.identifier.epage1051-
dc.identifier.isiWOS:000439570500015-
dc.publisher.placeUnited States-
dc.identifier.issnl1079-5642-

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