Abnormal function of aberrantly spliced ryanodine receptor and altered splicing in myotonic dystrophy brain.

• Project/Area Number: 19591019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Hyogo College of Medicine
• Principal Investigator: YOSHIKAWA Hiroo Hyogo College of Medicine, 医学部, 教授 (90273680)
• Co-Investigator(Kenkyū-buntansha): KIMURA Takashi 兵庫医科大学, 医学部, 講師 (20441264)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 筋強直性ジストロフィー / スプライシング異常 / リアノジン受容体 / NMDA型グルタミン酸受容体 / Ca^<2+> / カルモジュリン依存性プロテインキナーゼII / 筋強直性ジストロフィー症 / スプライシング

Research Abstract

筋強直性ジストロフィー患者において、以前に我々が報告したリアノジン受容体スプライシング異常が、安静時、興奮時のCa^<2+>代謝に異常を生じさせることを新たに見出した。脳、心筋でのスプライシング異常を解析し、心筋ではリアノジン受容体タイプ2の新規スプライシング異常、脳ではリアノジン受容体タイプ1、NMDA型グルタミン酸受容体、およびCa^<2+>/カルモジュリン依存性プロテインキナーゼIIの新規スプライシング異常を見出した。

Research Products

• [Journal Article] Alternative splicing of RyR1 alters the efficacy of skeletal EC coupling. (2009)
  • Author(s): Kimura T, Lueck JD, Harvey PJ, Pace SM, Ikemoto N, Casarotto MG, Dirksen RT, Dulhunty AF.
  • Journal Title: Cell Calcium 45 Pages: 264-74
• [Journal Article] Alternative splicing of RyRl alters the efficacy of skeletal EC coupling. (2009)
  • Author(s): Kimura T, Lueck JD, Harvey PJ, Pace SM, Ikemoto N, Casarotto MG, D irksen RT, Dulhunty AF
  • Journal Title: Cell Calcium 45 Pages: 264-74
  • Peer Reviewed
• [Journal Article] Phosphorylation of skeletal muscle calsequestrin enhances its Ca(2+) binding capacity and promotes its association with junctin. (2008)
  • Author(s): Beard NA, Wei L, Cheung SN, Kimura T, Varsanyi M, Dulhunty AF.
  • Journal Title: Cell Calcium 44 Pages: 363-73
  • Peer Reviewed
• [Journal Article] Muscle-specific GSTM2-2 on the luminal side of the sarcoplasmic reticulum modifies RyR ion channel activity. (2008)
  • Author(s): Wei L, Abdellatif YA, Liu D, Kimura T, 以下5名省略
  • Journal Title: Int J Biochem Cell Biol. 40 Pages: 1616-28
  • Peer Reviewed
• [Journal Article] Aberrantly spliced alpha-dystrobrevin alters alpha-syntrophin binding in myotonic dystrophy type 1. (2008)
  • Author(s): Nakamori M, Kimura T, 以下6名省略
  • Journal Title: Neurology 70 Pages: 677-85
  • Peer Reviewed
• [Journal Article] Circulating CD34-positive cells provide a marker of vascular risk associated with cognitive impairment. (2008)
  • Author(s): Taguchi A, Matsuyama T, Nakagomi T, Shimizu Y, Fukunaga R, Tatsumi Y, Yoshikawa H, 以下6名省略
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism 28 Pages: 445-449
  • Peer Reviewed
• [Journal Article] Increasing in circulating CD34-positive cells in patients with angiographic evidence of moyamoya-like vessels. (2008)
  • Author(s): Yoshihara T, Taguchi A, Matsuyama T, Shimizu Y, Kikuchi-Taura A, Soma T, Stern DM , Yoshikawa H,以下4名省略
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism. 28 Pages: 1086-89
  • Peer Reviewed
• [Journal Article] Mice lacking the schizophrenia-associated protein FEZ-1 manifest hyperactivity and enhanced responsiveness to psychostimulants. (2008)
  • Author(s): Sakae N, Yamasaki N, Tsukada T, Yamada M, Yoshikawa H, 以下6名省略
  • Journal Title: Hum Mol Genet. 17 Pages: 3191-203
  • Peer Reviewed
• [Journal Article] Pioglitazone promotes peripheral nerve remyelination after crush injury through CD36 upregulation. (2008)
  • Author(s): Eto M, Sumi H, Fujimura H, Yoshikawa H, Sakoda S,
  • Journal Title: J Peripher Nerv Syst. 13 Pages: 242-8
  • Peer Reviewed
• [Journal Article] Phosphorylation of skeletal muscle calsequestrin enhances its Ca2+binding capacity and promotes its association with junctin. (2008)
  • Author(s): Beard NA, Wei L, Cheung SN, Kimura T, Varsanyi M, Dulhunty AF
  • Journal Title: Cell Calcium 44 Pages: 363-73
  • Peer Reviewed
• [Journal Article] A variably spliced region in the type 1 ryanodine receptor may participate in an inter-domain interaction. (2007)
  • Author(s): Kimura T, Pace SM, Wei L, Beard NA, Dirksen RT, Dulhunty AF.
  • Journal Title: Biochem J. 401 Pages: 317-24
  • Peer Reviewed
• [Journal Article] Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling. (2007)
  • Author(s): Goonasekera SA, Beard NA, Groom L, Kimura T, 以下5名省略
  • Journal Title: J Gen Physiol. 130 Pages: 365-78
  • Peer Reviewed
• [Journal Article] Altered mRNA splicing of dystrophin in type 1 myotonic dystrophy. (2007)
  • Author(s): Nakamori M, Kimura T, Fujimura H, Takahashi MP, Sakoda S.
  • Journal Title: Muscle Nerve. 36 Pages: 251-7
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle (2007)
  • Author(s): Ikezoe K, Nakamori M, Furuya H, Arahata H, Kanemoto S, Kimura T, 4名省略, Kira J.
  • Journal Title: Acta Neuropathol. 114 Pages: 527-35
  • Peer Reviewed
• [Journal Article] Nonmyelinating Schwann cell involvement with well preserved unmyelinated axons inCMT1A. (2007)
  • Author(s): Koike H, Iijima M, Mori K, Yamamoto M, Hattori N, Katsuno M, Tanaka F, Watanabe H, Doyu M, Yoshikawa H,, Sobue G.
  • Journal Title: J Neuropathol Exp Neurol. 66 Pages: 1027-1036
  • Peer Reviewed
• [Journal Article] Recognition memory for unfamiliar faces in Parkinson's disease: Behavioral and electrophysiologic measures. (2007)
  • Author(s): Kida Y, Tachibana H, Takeda M, Yoshikawa H, Okita T.
  • Journal Title: Parkinsonism and Related disorders. 13 Pages: 157-164
  • Peer Reviewed
• [Journal Article] inad マウスにおける末梢神経病変 (2007)
  • Author(s): 辰巳美晶、辰己由記、芳川浩男
  • Journal Title: 末梢神経 Peripheral Nerve. 18 Pages: 53-60
  • NAID: 10027577928
  • Peer Reviewed
• [Presentation] 筋強直性ジストロフィー症におけるα-dystrobrevin スプライシング異常 (2008)
  • Author(s): 高橋正紀, 中森雅之, 木村卓, 久保田智哉, 松村剛, 隅寿恵, 藤村晴俊, 佐古田三郎
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] 筋強直性ジストロフィー脳、心筋におけるスプライシング異常の検討 (2008)
  • Author(s): 木村卓, 中森雅之, 高橋正紀, 松村剛, 藤村晴俊, 陣内研二, 芳川浩男
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] 筋強直性ジストロフィー症におけるα-dystrobrevinスプライシング異常 (2008)
  • Author(s): 高橋正紀(大阪大学神経内科), 中森雅之, 木村卓, 久保田智哉, 松村剛, 隅寿恵, 藤村晴俊, 佐古田三郎
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] A variably spliced region of Ryanodine receptor 1 may be involved in excitation-contraction coupling. (2007)
  • Author(s): Kimura, T., Nakamori, M., Takahashi, M. P., Yoshikawa, H., Sakoda, S., and Dulhunty, A. F.
  • Organizer: 6^<th> International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: イタリア、ミラノ
• [Presentation] 筋強直性ジストロフィー症にみられるリアノジン受容体機能異常のメカニズム (2007)
  • Author(s): 木村卓, 中森雅之, 高橋正紀, Dulhunty Angela F., 芳川浩男, 佐古田三郎
  • Organizer: 第48回日本神経学会総会
• [Presentation] 筋強直性ジストロフィー症にみられるリアノジン受容体機能異常のメカニズム (2007)
  • Author(s): 木村 卓, 中森 雅之, 高橋 正紀, Dulhunty Angela F., 芳川 浩男, 佐古田 三郎
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] A variably spliced region of Ryanodine receptor 1 may be involved in excitation-contraction coupling (2007)
  • Author(s): Kimura, T., Nakamori, M., Takahashi, M. P., Yoshikawa, H., Sakoda, S., Dulhunty, A. F.
  • Organizer: 6th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: イタリア、ミラノ
• [Book] 【処方計画法】神経・筋疾患低K性周期性四肢麻痺(解説/特集) (2008)
  • Author(s): 木村卓
  • Total Pages: 688
  • Publisher: 永井書店