Elucidation of the physiological function of dysferlin in sarcolemmal repair

• Project/Area Number: 18590966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: MATSUDA Chie National Institute of Advanced Industrial Science and Technology, 脳神経情報研究部門, 主任研究員 (50344099)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 脳神経疾患 / タンパク質 / 生体分子 / ディスフェルリン / 筋ジストロフィー / 膜修復 / アクチン細胸骨格 / アフィキシン / グアニンヌクレオチド交換因子 / アクチン細胞骨格

Research Abstract

ディスフェルリンの生理的意義を解明するために、結合タンパク質の探索を行いアフィキシンを同定した。アフィキシンはヒト正常骨格筋の細胞膜でディスフェルリンと共局在しているが、ディスフェルリンを欠損する筋ジストロフィー患者骨格筋では、部分的に細胞膜から欠落することを見出した。培養細胞を用いてアフィキシンの生理的機能を解析したところ、アクチン細胞骨格系の再構成を行うことを見出した。細胞骨格系の再構成は細胞膜の修復過程でも観察されることから、アフィキシンもディスフェルリンと共に筋細胞膜の修復に関与することが予測される。

Research Products

• [Journal Article] Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese LGMD1A (2009)
  • Author(s): Shalaby, S., et al
  • Journal Title: (In press)
  • Peer Reviewed
• [Journal Article] Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness (2008)
  • Author(s): Lawrence J. Hayward, Joanna S. Kim,Ming-Yang Lee, Hongru Zhou, Ji W. Kim,Kumudini Misra, Mohammad Salajegheh,Fen-fen Wu, Chie Matsuda, Valerie Reid,Didier Cros,Eric P. Hoffman, Jean -MarcRenaud, Stephen C. Cannon, and Robert H.Brown, Jr
  • Journal Title: J Clin Invest 118(4) Pages: 1437-1449
• [Journal Article] Affixin activates Rac1 via aPIX and bPIX in C2C12 myoblast (2008)
  • Author(s): Matsuda C, Kameyama K, Suzuki A, MishimaW, Yamaji S, Okamoto H, Nishino I and Hayashi YK
  • Journal Title: FEBS Letters 9;582(8) Pages: 1189-1196
• [Journal Article] Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive Weakness (2008)
  • Author(s): Hayward, J.L., et. al.
  • Journal Title: The Journal of Clinical Investigation (In press)
  • Peer Reviewed
• [Journal Article] Affixin activates Racl Via αPIX and βPIX (2008)
  • Author(s): Matsuda, C., et. al.
  • Journal Title: FEBS Letters (In press)
  • Peer Reviewed
• [Journal Article] Two Endoplasmic Reticulum-Associated Degradation Systems (ERAD) for the Novel Variant of the Mutant Dysferlin;Ubiquitin/Proteasome ERAD (I) and Autophagy/Lysosome ERAD (II) (2007)
  • Author(s): Fujita E, Kouroku Y, Isoai A, Kumagai H, Mizutani A, Matsuda C, Hayashi YK, Momoi
  • Journal Title: Hum Mol Genet 16(5) Pages: 618-629
• [Journal Article] Two Endoplasmic Reticulum-Associated Degradation Systems (ERAD) for the Novel Variant of the Mutant Dysferlin; Ubiquitin/Proteasome ERAD (I) and Autophagy/Lysosome ERAD (II). (2007)
  • Author(s): Fujita E, Kouroku Y, Isoai A, Kumagai H, Mizutani A, Matsuda C, Hayashi YK, Momoi T.
  • Journal Title: Human Molecular Genetics. 16巻5号 Pages: 618-629
• [Journal Article] The gamma-parvin-integrin-linked kinasecomplex is critically involved in leukocyte-substrate interaction (2006)
  • Author(s): Yoshimi R, Yamaji S, Suzuki A, Mishima W, Okamura M, Obana T, Matsuda C, Miwa Y, OhnoS, Ishigatsubo Y
  • Journal Title: J Immunol 15; 176(6) Pages: 3611-3624
• [Journal Article] Dysferlin interacts with affixin(beta-parvin) at the sarcolemma (2005)
  • Author(s): Matsuda C, Kameyama K, Tagawa K, Ogawa M,Suzuki A, Yamaji S, Okamoto H, Nishino I, Hayashi YK
  • Journal Title: J Neuropathol Exp Neurol 64(4) Pages: 334-340
• [Presentation] Altered interaction of mutant lamin A and barrier to autointegration factor (BAF) (2008)
  • Author(s): 松田知栄
  • Organizer: 13^<th> World Muscle Society
  • Place of Presentation: Newcastle, England
  • Year and Date: 2008-09-30
• [Presentation] Altered Interaction of mutant lamin A and barrier to autointegration factor (BAF) (2008)
  • Author(s): Matsuda C , Kameyama K, Nishino I and Hayashi YK
  • Organizer: 12th International Congress of World Muscle Society
  • Place of Presentation: Newcastle upon Tyne, UK
  • Year and Date: 2008-09-29
• [Presentation] Affixin activates Racl via PIX inC2C12 myoblasts (2007)
  • Author(s): 松田 知栄
  • Organizer: 12th World Muscle Society
  • Place of Presentation: Sicily, Italy
  • Year and Date: 2007-10-18
• [Presentation] Affixin activates Rac1 via aPIX and bPIXin C2C12 myoblast (2007)
  • Author(s): Matsuda C, KameyamaK, Suzuki A, Mishima W, Yamaji S, Okamoto H, Nishino I and Hayashi YK
  • Organizer: 12th International Congress of World Muscle Society
  • Place of Presentation: Taormina, Italy
• [Presentation] Dysferlin interacts with affixin (beta-parvin) at the sarcolemma (2006)
  • Author(s): Matsuda C, Kameyama K, Nishino I, Hayashi YK
  • Organizer: XI International Congress on Neuromuscular diseases
  • Place of Presentation: Istanbul, Turkey