title: Clot retraction is mediated by factor XIII-dependent fibrin-αIIbβ3-myosin axis in platelet sphingomyelin-rich membrane rafts.
abstract: Membrane rafts are spatially and functionally heterogenous in the cell membrane. We observed that lysenin-positive sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin and myosin are colocalized on activation by thrombin. The clot retraction of SM-depleted platelets from SM synthase knockout mouse was delayed significantly, suggesting that platelet SM-rich rafts are involved in clot retraction. We found that fibrin converted by thrombin translocated immediately in platelet detergent-resistant membrane (DRM) rafts but that from Glanzmann's thrombasthenic platelets failed. The fibrinogen γ-chain C-terminal (residues 144-411) fusion protein translocated to platelet DRM rafts on thrombin activation, but its mutant that was replaced by A398A399 at factor XIII crosslinking sites (Q398Q399) was inhibited. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. In the cytoplasm, myosin translocated concomitantly with fibrin translocation into the DRM raft of thrombin-stimulated platelets. Furthermore, the disruption of SM-rich rafts by methyl-β-cyclodextrin impaired myosin activation and clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbβ3-myosin complex is formed as a primary axis to promote platelet contraction.
authors.affiliation: Laboratory of Biomembrane and.
authors.forename: Kohji
authors.initials: K
authors.lastname: Kasahara
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kaneda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Miki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Iida
authors.forename: Naoko
authors.initials: N
authors.lastname: Sekino-Suzuki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawashima
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimonaka
authors.forename: Morio
authors.initials: M
authors.lastname: Arai
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ohno-Iwashita
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Abe
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Souri
authors.forename: Akitada
authors.initials: A
authors.lastname: Ichinose
authors.forename: Naomasa
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003018:Clot Retraction / Q000187:drug effects / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics / Q000378:metabolism*; D005337:Fibrin / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D013109:Sphingomyelins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency / Q000235:genetics
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013109:Sphingomyelins; D005337:Fibrin; D005176:Factor XIII; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D013917:Thrombin; D009218:Myosins