title: Palladin is involved in platelet activation and arterial thrombosis.
abstract: The dynamics of actin cytoskeleton have been shown to play a critical role during platelet activation. Palladin is an actin-associated protein, serving as a cytoskeleton scaffold to bundle actin fibers and actin cross linker. The functional role of palladin on platelet activation has not been investigated. Here, we characterized heterozygous palladin knockout (palladin+/-) mice to elucidate the platelet-related functions of palladin. The results showed that palladin was expressed in platelets and moderate palladin deficiency accelerated hemostasis and arterial thrombosis. The aggregation of palladin+/-platelets was increased in response to low levels of thrombin, U46619, and collagen. We also observed enhanced spreading of palladin+/-platelets on immobilized fibrinogen (Fg) and increased rate of clot retraction in platelet-rich plasma (PRP) containing palladin+/-platelets. Furthermore, the activation of the small GTPase Rac1 and Cdc42, which is associated with cytoskeletal dynamics and platelet activation signalings, was increased in the spreading and aggregating palladin+/-platelets compared to that in wild type platelets. Taken together, these findings indicated that palladin is involved in platelet activation and arterial thrombosis, implying a potent role of palladin in pathophysiology of thrombotic diseases.
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China; Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, SJTUSM, Shanghai 200025, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China; Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, SJTUSM, Shanghai 200025, China.
authors.forename: Panlai
authors.initials: P
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China; Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Xiyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, SJTUSM, Shanghai 200025, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, SJTUSM, Shanghai 200025, China; Shanghai Research Center for Model Organisms, Shanghai 201203, China. Electronic address: suyingdang@shsmu.edu.cn.
authors.forename: Suying
authors.initials: S
authors.lastname: Dang
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China; Shanghai Research Center for Model Organisms, Shanghai 201203, China. Electronic address: zhugangw@shsmu.edu.cn.
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015539:Platelet Activation; D053657:Platelet-Rich Plasma / Q000166:cytology / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C581598:Cdc42 protein, mouse; D003598:Cytoskeletal Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C484602:Rac1 protein, mouse; C485873:palladin protein, mouse; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
keywords: Cdc42; Knockout mice; Paladin; Platelet activation; Rac1