1994 年度実績報告書

神経細胞.細胞骨格の分子細胞生物学的研究

研究課題

研究課題/領域番号	04102005
研究機関	東京大学
研究代表者	廣川信隆東京大学, 医学部(医), 教授 (20010085)
研究分担者	吉武玲子 , 医学部, 助手 (40230718) 金井克光 , 医学部, 助手 (80214427) 田中隆夫医学部, 講師 (50218004) 竹村玲子沖中記念成人病研究所, 研究員 (50171674)
キーワード	神経細胞 / 細胞骨格 / 分子細胞生物学 / 細胞の形態形成 / 物質輸送 / 微小管関連蛋白 / 微小管結合性モーター分子 / KIFs
研究概要	1)神経細胞の形態形成における細胞骨格の機能。(1)Tau遺伝子欠失マウスの分子細胞生物学的研究を行い、Tauか細い軸索の微小管の安定化とorganizationに重要な役割をはたしている事を明らかにした。(2)神経細胞の極性の基礎となるMAPsの局在化機構を、標識'付MAP2,およびTan cDNA又そのキメラやdeletion mutant cDNAの初代培養神経細胞への形質導入により解析し、MAP2の軸索内移行の阻害と微小管の結合性の違いによる軸索、及び樹状突起への局在化の機構がある事を明らかにした。 2)神経細胞内の物質輸送における細胞骨格の機能。(1)新しい微小管結合性モーター分子群KIFsの内、K1F1A,KIFIB,KIF2,KIF3A,KIF4の分子細胞生物学的解析を行った。その結果、KIFIAはモノマーで順行性にシナプス小胞の前駆体を1.2μm/secの最も速い速度で運ぶモーターであり、KIFIBはやはりモノマ一で順行性にミトコンドリアを0.5μm/secの速度で運び、KIF3AはKIF3Bとへテロダイマーを形成し、0.4μm/secでシナプス小胞の前駆体でないおそらく形質膜の前駆体を順行性に運ぶモーターである事か分かった。又、KIF2とKIF4はその発現が発達段階により制御されるモーター分子で、K1F2は中央にモーター領域のあるホモダイマーで幼若な神経細胞でシナプス小胞の前駆体ではない膜小器官を順行性に運び、KIF4は頭部と尾部よりなる120nm長のホモダイマーでKIF2より幼若な時期に発現され、神経成長端に存在する小胞を0.2μm/secで順行性に運ぶモーターである事か判明した。以上の結果から特にKIFIAとKIFIBは、初めて運ぶ膜小器官が明らかなモーターとなり、又モノマーで働くユニークなモーターである事が明らかとなった。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] Hirokawa,N.: "Microtubule organization and dynaics on Microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-83 (1994)
[文献書誌] Hagiwara,H.et al.: "Compe′tition between motor molecules (Kinesin and cytoplasmic dynein)and fibrous microtubule-associated proteins in binding to microtubules" Journal of Biological Chemistry. 269. 3581-3589 (1994)
[文献書誌] MIki,H.et al.: "Association of Ash/Grb-2 with dynamin through the Src homology 3 domain" Journal of Biological Chemistry. 269. 5489-5492 (1994)
[文献書誌] Hisanaga,S.et al.: "Phosporylation of native and reassembled neurofilaments composed of NF-L.NF-M.and NF-H by the catalytic subunits of cAMP-dependent orotein kinase" Molecular Biology of the Cell. 5. 161-172 (1994)
[文献書誌] Harada,A.et al.: "Altered microtubule orgnization in small-calibro xons of mice lacking tau protein" Nature. 36. 488-491 (1994)
[文献書誌] Kondo,S.et al.: "KIF3A is a new microtubules based fast anterograde motor in the nerve axons21GC06:Journal of Cell Biology" 125. 1095-1107 (1994)
[文献書誌] Sekine,Y.et al.: "A novel microtubule-based motor protein (KIF4)for organelle transports whose expression is regulated developmentally21GC07:Journal of Cell Biology" 127. 187-202 (1994)
[文献書誌] Ando,A.et al.: "A complex of GRB2-dynamin binds to tyrosine-phosphoryated insulin receptor suhstrate-1 after insulin treatment" ENBO Journal. 13. 3033-3038 (1994)
[文献書誌] TAkeda,S.et al.: "DIfferential dynamics of neurofilament H protein and neurofilament I,protein in neuron" Journal of Cell Biology. 127. 173-186 (1994)
[文献書誌] Kikkawa,M.et al.: "Direct visualization of the microtubule lattice seam both in vitro and in vivo" Journal of Cell Biology. 127. 1965-1971 (1994)
[文献書誌] Hayashi,T.et al.: "Redistribution of synapsin 1 and synaptophysin in response to elec-trical stimulation in the rat neurohypophysial nerve" Cell Strueture and Function. 19. 253-262 (1994)
[文献書誌] Nangaku,M.et al.: "KIF1B;Anew microtubule plus-end directed monomeric for mitochondria transport" Cell. 39. 1209-1220 (1994)
[文献書誌] Kanai,Y.and N.Hirokawa: "Sorting mechanisma tau and MAP2 inneuron : suppressed axonal transport of MAP2 and Locally regulated microtubule binding" Neuron. (in press). (1995)
[文献書誌] Nakagawa,T.et al.: "Two distinct functions of the carboxyl temonal tail domain of NF-M upon neurofilament assembly; crossbridge foramtion and longitudinal streching of filaments21GC14:Journal of Cell Biology" (in press). (1994)
[文献書誌] Okada,Y.et al.: "The activation of protein kinase A pathway selectively inhibits anterograde axonal of vesicles hut not mitochondria trans-port nr retrogradr transport in vito" Journal of Neuroscience. (in press). (1995)
[文献書誌] Noda,Y.et al.: "KIF2 is a new anterograde microtubule based motor which transports membranous organelles distinct from those carried by KHC or KIF3A/B" Journal of Cell Biology. (in press). (1995)

1994 年度 実績報告書

神経細胞.細胞骨格の分子細胞生物学的研究

研究代表者

廣川 信隆 東京大学, 医学部(医), 教授 (20010085)

研究成果

[文献書誌] Hirokawa,N.: "Microtubule organization and dynaics on Microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-83 (1994)

[文献書誌] Hagiwara,H.et al.: "Compe′tition between motor molecules (Kinesin and cytoplasmic dynein)and fibrous microtubule-associated proteins in binding to microtubules" Journal of Biological Chemistry. 269. 3581-3589 (1994)

[文献書誌] MIki,H.et al.: "Association of Ash/Grb-2 with dynamin through the Src homology 3 domain" Journal of Biological Chemistry. 269. 5489-5492 (1994)

[文献書誌] Hisanaga,S.et al.: "Phosporylation of native and reassembled neurofilaments composed of NF-L.NF-M.and NF-H by the catalytic subunits of cAMP-dependent orotein kinase" Molecular Biology of the Cell. 5. 161-172 (1994)

[文献書誌] Harada,A.et al.: "Altered microtubule orgnization in small-calibro xons of mice lacking tau protein" Nature. 36. 488-491 (1994)

[文献書誌] Kondo,S.et al.: "KIF3A is a new microtubules based fast anterograde motor in the nerve axons21GC06:Journal of Cell Biology" 125. 1095-1107 (1994)

[文献書誌] Sekine,Y.et al.: "A novel microtubule-based motor protein (KIF4)for organelle transports whose expression is regulated developmentally21GC07:Journal of Cell Biology" 127. 187-202 (1994)

[文献書誌] Ando,A.et al.: "A complex of GRB2-dynamin binds to tyrosine-phosphoryated insulin receptor suhstrate-1 after insulin treatment" ENBO Journal. 13. 3033-3038 (1994)

[文献書誌] TAkeda,S.et al.: "DIfferential dynamics of neurofilament H protein and neurofilament I,protein in neuron" Journal of Cell Biology. 127. 173-186 (1994)

[文献書誌] Kikkawa,M.et al.: "Direct visualization of the microtubule lattice seam both in vitro and in vivo" Journal of Cell Biology. 127. 1965-1971 (1994)

[文献書誌] Hayashi,T.et al.: "Redistribution of synapsin 1 and synaptophysin in response to elec-trical stimulation in the rat neurohypophysial nerve" Cell Strueture and Function. 19. 253-262 (1994)

[文献書誌] Nangaku,M.et al.: "KIF1B;Anew microtubule plus-end directed monomeric for mitochondria transport" Cell. 39. 1209-1220 (1994)

[文献書誌] Kanai,Y.and N.Hirokawa: "Sorting mechanisma tau and MAP2 inneuron : suppressed axonal transport of MAP2 and Locally regulated microtubule binding" Neuron. (in press). (1995)

[文献書誌] Nakagawa,T.et al.: "Two distinct functions of the carboxyl temonal tail domain of NF-M upon neurofilament assembly; crossbridge foramtion and longitudinal streching of filaments21GC14:Journal of Cell Biology" (in press). (1994)

[文献書誌] Okada,Y.et al.: "The activation of protein kinase A pathway selectively inhibits anterograde axonal of vesicles hut not mitochondria trans-port nr retrogradr transport in vito" Journal of Neuroscience. (in press). (1995)

[文献書誌] Noda,Y.et al.: "KIF2 is a new anterograde microtubule based motor which transports membranous organelles distinct from those carried by KHC or KIF3A/B" Journal of Cell Biology. (in press). (1995)

1994 年度実績報告書

廣川信隆東京大学, 医学部(医), 教授 (20010085)