Fibrin translocation to platelet membrane rafts in blood coagulation

• Project/Area Number: 23570182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KASAHARA Kohji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副室長 (60250213)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ラフト / 血小板 / フィブリン / 血液凝固

Outline of Final Research Achievements

We observed that sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin is 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. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. Furthermore, the disruption of SM-rich rafts by methyl-β-cyclodextrin impaired clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbβ3 complex is formed as a primary axis to promote platelet contraction.

Research Products

• [Journal Article] Update Review血小板による血栓形成メカニズム研究の最新動向 (2014)
  • Author(s): 笠原浩二 山本正雅
  • Journal Title: 実験医学 Volume: 32 Pages: 2966-2971
  • Peer Reviewed
• [Journal Article] Fibrin-translocation to platelet lipid rafts and clot retraction (2014)
  • Author(s): Kasahara K
  • Journal Title: Japanese Journal of Thrombosis and Hemostasis Volume: 25 Issue: 1 Pages: 92-94
  • DOI: 10.2491/jjsth.25.92
  • NAID: 130003393345
  • ISSN: 0915-7441, 1880-8808
  • Peer Reviewed
• [Journal Article] Introduce My Article (2014)
  • Author(s): 笠原浩二
  • Journal Title: Rinsho Ketsueki Volume: 55 Issue: 3 Pages: 366-367
  • DOI: 10.11406/rinketsu.55.366
  • NAID: 130004724859
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Clot retraction is mediated by factor XIII-dependent fibrin-aIIbb3-myosin axis in platelet sphingomyelin-rich membrane rafts (2013)
  • Author(s): Kasahara, K., Kaneda, M., Miki, T., Iida, K., Sekino-Suzuki, N., Kawashima, I., Suzuki, H., Shimonaka, M., Arai, M., Ohni-Iwashita, Y., Kojima, S., Abe, M., Kobayashi, T., Okazaki, T., Souri, M., Ichinose, A., Yamamoto, N.
  • Journal Title: Blood Volume: 122(19) Issue: 19 Pages: 3340-3348
  • DOI: 10.1182/blood-2013-04-491290
  • Peer Reviewed
• [Journal Article] An anti-sulfatide antibody O4 immunoprecipitates sulfatide rafts including Fyn, Lyn and the G protein alpha subunit in rat primary immature oligodendrocytes. (2013)
  • Author(s): Miki, T., Kaneda, M., Iida, K., Hasegawa, G., Murakami, M., Yamamoto, N., Asou, H., Kasahara, K.
  • Journal Title: Glycoconj. J. Volume: 30(9) Issue: 9 Pages: 819-823
  • DOI: 10.1007/s10719-013-9487-5
  • Peer Reviewed
• [Journal Article] Change of dynamics of raft-model membrane induced by amyloid-beta protein binding (2013)
  • Author(s): Hirai, M., Kimura, R., Takeuchi, K., Sugiyama, M., Kasahara, K., Ohta, N., Farago, B., Stadler, A., Zaccai, G.
  • Journal Title: Eur.Phys.J.E.Soft Matter Volume: 36(7) Issue: 7 Pages: 9887-9887
  • DOI: 10.1140/epje/i2013-13074-3
  • Peer Reviewed
• [Journal Article] Involvement of gangliosides in the process of Cbp/PAG phosphorylation by Lyn in developing cerebellar growth cones (2013)
  • Author(s): Sekino-Suzuki N, Yuyama K, Yamamoto T. (10名)
  • Journal Title: J Neurochem Volume: Vol.124 Issue: 4 Pages: 514-522
  • DOI: 10.1111/jnc.12040
  • Peer Reviewed
• [Journal Article] Novel Bernard-Soulier syndrome variants caused by compound heterozygous mutations (case I) or a cytoplasmic tail truncation (case II) of GPIba. (2013)
  • Author(s): Yamamoto N, Akamatsu N, Sakuraba H, Matsuno K, Hosoya R, Nogami H, Kasahara K, Mituyama S, Arai M
  • Journal Title: Thromb. Res. Volume: 131 Issue: 4 Pages: e160-e167
  • DOI: 10.1016/j.thromres.2013.01.014
  • Peer Reviewed
• [Journal Article] 三量体Gタンパク質Goaの糖脂質ミクロドメインにおけるシグナル伝達 (2012)
  • Author(s): 三木俊明、兼田瑞穂、*笠原浩二
  • Journal Title: 膜 Volume: 37 Pages: 168-173
  • Peer Reviewed
• [Journal Article] Ganglioside GD3 monoclonal antibody-induced paxillin tyrosine phosphorylation and filamentous actin assembly in cerebellar growth cones. (2011)
  • Author(s): Yuyama K, Sekino-Suzuki N, Yamamoto N, Kasahara K
  • Journal Title: J.Neurochem. Volume: 116 Issue: 5 Pages: 845-850
  • DOI: 10.1111/j.1471-4159.2010.07071.x
  • Peer Reviewed
• [Presentation] Clot retraction is mediated by factor XIII-dependent fibrin -alphaIIbbeta3 –myosin (2014)
  • Author(s): Kasahara K
  • Organizer: BIT’s 5th World Gene Convention
  • Place of Presentation: Haikou, China
  • Year and Date: 2014-11-13 – 2014-11-16
  • Invited
• [Presentation] フィブリンの血小板脂質ラフト移行と血餅退縮 (2014)
  • Author(s): 笠原浩二
  • Organizer: 第19回近畿血栓症研究会
  • Place of Presentation: 北浜フォーラム（大阪市中央区）
  • Year and Date: 2014-10-11
• [Presentation] Analysis of neural raft signaling by anti-glycosphingolipid antibody. (2014)
  • Author(s): Kasahara K
  • Organizer: International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji
• [Presentation] Clot retraction is mediated by factor XIII-dependent fibrin-aIIbb3-myosin axis in platelet sphingomyelin-rich membrane rafts. (2014)
  • Author(s): Kasahara K, Ichinose A, Yamamoto N.
  • Organizer: Keystone Symposia "New Frontier in the Discovery and Treatment of Thrombosis"
  • Place of Presentation: Colorado, USA
• [Presentation] Clot retraction is mediated by factor XIII-dependent fibrin-aIIbb3-myosin axis in platelet sphingomyelin-rich membrane rafts (2014)
  • Author(s): Kasahara K
  • Organizer: 58th Annual Meeting Society of Thrombosis and Haemostasis Research
  • Place of Presentation: Vienna, Austria
• [Presentation] Involvement of Ganglioside GD3-raft Signaling in the Growth Cone Behavior of Cerebellar Granule Neurons (2013)
  • Author(s): Kasahara K
  • Organizer: 22th International Symposium on Glycoconjugates (Glyco22)
  • Place of Presentation: Dalian, China
• [Presentation] 神経系ラフトシグナルの抗糖脂質抗体による解析 (2013)
  • Author(s): 笠原浩二、兼田瑞穂、飯田和子、阿相皓晃、三木俊明
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪
• [Presentation] カルレティキュリンのプロテインジスルフィドイソメラーゼ活性の検討 (2013)
  • Author(s): 長谷川豪、斉藤佑尚、笠原浩二
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] 血液凝固XIII因子によるフィブリンの血小板スフィンゴミエリンラフト移行と血餅退縮 (2013)
  • Author(s): 笠原浩二
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Fibrin-associated platelet rafts function as platform for clot retraction. (2012)
  • Author(s): Kasahara K
  • Organizer: Gordon Research Conference “Glycolipid & Spingolipid Biology”
  • Place of Presentation: イタリア
• [Presentation] Translocation of fibrin and myosin into platelet membrane rafts is an important process for clot retraction via a functional property of GPIIb/IIIa. (2011)
  • Author(s): Kasahara K, Kaneda M, Miki T, Iida K, Suzuki H, Hara Y, Shimonaka M, Arai M, Kobayashi T, Ichinose A, Yamamoto N
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis.
  • Place of Presentation: 京都
• [Presentation] 血小板の血液凝固第XIII因子基質としてのビンキュリン分解産物 (2011)
  • Author(s): 原裕太、兼田瑞穂、三木俊明、林もゆる､下仲基之、山本正雅、笠原浩二
  • Organizer: 日本生化学会関東支部例会
  • Place of Presentation: 東京
• [Presentation] Fibrin-integrin-myosin signaling axis in platelet membrane rafts (2011)
  • Author(s): Kasahara K
  • Organizer: The 30th NAITO conference on membrane dymanics and lipid biology [II]
  • Place of Presentation: 札幌
• [Presentation] 糖脂質マイクロドメインを介するシグナル伝達による生体制御
  • Author(s): 笠原浩二
  • Organizer: 日本膜学会第34年会生体膜シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] 細胞膜ラフトにおける機能分子の集積とその意義
  • Author(s): 笠原浩二
  • Organizer: 第27回日本動物細胞工学シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] 血小板スフィンゴミエリン特異的ラフトへのフィブリン移行と血餅退縮
  • Author(s): 笠原浩二、兼田瑞穂、三木俊明、飯田和子、小林俊秀、岡崎俊朗、山本正雅
  • Organizer: 第７回スフィンゴテラピイ研究会
  • Place of Presentation: 能登
• [Presentation] 血小板スフィンゴミエリン特異的膜ラフトへのフィブリン移行と血餅退縮
  • Author(s): 笠原浩二、兼田瑞穂、三木俊明、飯田和子、鈴木英紀、小林俊秀、岡崎俊朗、一瀬白帝、山本正雅
  • Organizer: ３４回日本血栓止血学会学術集会
  • Place of Presentation: 東京
• [Book] 実験医学 (2011)
  • Author(s): 笠原浩二
  • Total Pages: 3
  • Publisher: Campus&Conference探訪記 ISTH2011 KYOTO JAPAN
• [Remarks] 細胞膜研究室ホームページ
  • URL: http://www.igakuken.or.jp/biomembrane/
• [Remarks] 東京都医学総合研究所 細胞膜研究室
  • URL: http://www.igakuken.or.jp/biomembrane/