1999 Fiscal Year Annual Research Report

raftによる神経細胞の分化・生存のシグナルの調節機構の解明

Research Project

Project/Area Number	11159203
Research Institution	福井医科大学
Principal Investigator	武藤多津郎福井医科大学, 医学部・附属病院, 講師 (60190857)
Co-Investigator(Kenkyū-buntansha)	得田彰福井医科大学, 医学部・附属病院, 助手 (30303374) 栗山勝福井医科大学, 医学部, 教授 (80107870)
Keywords	GM1ガングリオシド / Trk / 神経栄養因子 / チロシンキナーゼ / カヴェオラ
Research Abstract	我々は、これまで神経疾患の新しい治療法開発を目指して種々の検討をしてきた。神経系組織の分化生存に必須の役割を果たすNGFをはじめとする神経栄養因子に着目し、その細胞内情報伝達を活性化させる内因性生理物質の探索をおこなってきており、神経細胞膜中のカヴェオラ(CV)という特殊な構造物中に多量に存在するGM1ガングリオシド(GM1)が神経栄養因子受容体のTrkを活性化させること、またその作用はGM1とTrkが強固に結合することが必要であることを見つけてきた。本年度の本研究では1)Trk中のGM1結合部位の同定、2)その結合部位を欠くdeletion mutant cDNAの作成とそのstable transfectantを作成し、3そのstable transfectant中のTrkのプロセッシングヘの影響とCV形成に対する影響を明らかにすることを目的に実験を進めた。その結果、1)GM1の結合部位はTrkのjuxtamembraneのextracellular側の糖鎖付加部位近辺であること、2)この結合部位を欠くdeletion mutantのTrkは細胞内プロセッシングに異常を来し正常に細胞膜にtargettingされないこと、またこの変異TrkはNGFに反応せず常に活性化された状態になっていることを見い出した(論文投稿中)。この結果をもとに、こうした変異Trkを発現する細胞系を用いて、CV機能に及ぼす影響を明らかにすると共にTrk始点とする細胞内情報伝達系への作用を主にキナーゼカスケードの観点から明らかにした。

Research Products

(8 results)

All Other

All Publications (8 results)

[Publications] Mutoh T, Kumano T, Nakagawa H, Kuriyama M.: "Involvement of tyrosine phosphorylation and in HMG-CoA reductase inhibitor-induced cell death of L6 myoblasts"FEBS Lett.. 444. 85-89 (1999)
[Publications] Mutoh T, Kumano T, Nakagawa H, Kuriyama M.: "Role of tyrosine phospho-rylaiton of phospholipase C-γ1 in the signal transduction pathway of HMG-CoA reductase inhibitor-induced cell death in L6 myoblasts"FEBS Lett.. 446. 91-94 (1999)
[Publications] Mitsuma N, Yamamoto M, Li M, Ito Y, Mitsuma T, Mutoh T, Takahashi M, Sobue G.: "Expression of GDNF receptor (Ret and GDNFR-α) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis"Brain Res.. 820. 77-85 (1999)
[Publications] Hamano T, Mutoh T, Hirayama M, Kuriyama M.: "MRI findings of benign monomeric amyotrophy of lower limb"J. Neurol. Sci.. 165. 184-187 (1999)
[Publications] Mutoh T, Sobue G, Hamano T, Kuriyama M, Hirayama M, Yamamoto M, Mitsuma T.: "Decreased tyrosine phosphorylation of TrkB receptor in the spinal cords from the patients with amyotrophic lateral sclerosis"Neurochem. Res.. (in press).
[Publications] Hamano T, Mutoh T, Sugie H, Koga H, Kuriyama M.: "Phosphoglycerate kinase deficiency. An adult myopathic form with a novel mutation"Neurology. (in press).
[Publications] Kumano T, Mutoh T, Nakagawa H, Kuriyama M.: "HMG-CoA reductase inhibitor induces a transient activation of high affinity nerve growth factor receptor, Trk, and morphological differentiation withfatal outcome in PC12 cells"Brain Res.. (in press).
[Publications] Fukumoto S, Mutoh T, Hasegawa T, Miyazaki H, Okada M, Goto G, Furukawa K, Urano T, Furukawa K.: "GD3 synthase gene expression in PC12 cells resulted in the continuous activation of TrkA and ERK1/2, leading to enhanced proliferation"J. Biol. Chem.. (in press).

1999 Fiscal Year Annual Research Report

raftによる神経細胞の分化・生存のシグナルの調節機構の解明

Principal Investigator

武藤 多津郎 福井医科大学, 医学部・附属病院, 講師 (60190857)

Research Products

[Publications] Mutoh T, Kumano T, Nakagawa H, Kuriyama M.: "Involvement of tyrosine phosphorylation and in HMG-CoA reductase inhibitor-induced cell death of L6 myoblasts"FEBS Lett.. 444. 85-89 (1999)

[Publications] Mutoh T, Kumano T, Nakagawa H, Kuriyama M.: "Role of tyrosine phospho-rylaiton of phospholipase C-γ1 in the signal transduction pathway of HMG-CoA reductase inhibitor-induced cell death in L6 myoblasts"FEBS Lett.. 446. 91-94 (1999)

[Publications] Mitsuma N, Yamamoto M, Li M, Ito Y, Mitsuma T, Mutoh T, Takahashi M, Sobue G.: "Expression of GDNF receptor (Ret and GDNFR-α) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis"Brain Res.. 820. 77-85 (1999)

[Publications] Hamano T, Mutoh T, Hirayama M, Kuriyama M.: "MRI findings of benign monomeric amyotrophy of lower limb"J. Neurol. Sci.. 165. 184-187 (1999)

[Publications] Mutoh T, Sobue G, Hamano T, Kuriyama M, Hirayama M, Yamamoto M, Mitsuma T.: "Decreased tyrosine phosphorylation of TrkB receptor in the spinal cords from the patients with amyotrophic lateral sclerosis"Neurochem. Res.. (in press).

[Publications] Hamano T, Mutoh T, Sugie H, Koga H, Kuriyama M.: "Phosphoglycerate kinase deficiency. An adult myopathic form with a novel mutation"Neurology. (in press).

[Publications] Kumano T, Mutoh T, Nakagawa H, Kuriyama M.: "HMG-CoA reductase inhibitor induces a transient activation of high affinity nerve growth factor receptor, Trk, and morphological differentiation withfatal outcome in PC12 cells"Brain Res.. (in press).

[Publications] Fukumoto S, Mutoh T, Hasegawa T, Miyazaki H, Okada M, Goto G, Furukawa K, Urano T, Furukawa K.: "GD3 synthase gene expression in PC12 cells resulted in the continuous activation of TrkA and ERK1/2, leading to enhanced proliferation"J. Biol. Chem.. (in press).

武藤多津郎福井医科大学, 医学部・附属病院, 講師 (60190857)