1995 Fiscal Year Annual Research Report

神経細胞・細胞骨格の分子細胞生物学的研究

Research Project

Project/Area Number	04102005
Research Institution	The University of Tokyo
Principal Investigator	廣川信隆東京大学, 医学部(医), 教授 (20010085)
Co-Investigator(Kenkyū-buntansha)	吉武玲子東京大学, 医学部, 講師 (40230718) 中田隆夫東京大学, 医学部, 助教授 (50218004) 竹村玲子沖中記念老人病研究所, 研究員 (50171674) 金井克光東京大学, 医学部, 助教授 (80214427)
Keywords	微小管 / KIF_S / 軸索輸送 / 神経細胞 / キネシン / 微小管関連蛋白
Research Abstract	I)神経細胞の形態形成における細胞骨格の機能 (1)主要な微小管関連蛋白MAP2及びMAP1Bの機能の解明。MAP1B遺伝子欠失マウスを作成し,その脳の組織構築,神経細胞の微細構造,他の細胞骨格蛋白の発現量の解析を行った。MAP1B欠失マウスは運動性の低下,体重減少がみられ,特に視神経の発達が遅延していた。MAP1Bが軸索伸長時に重要な役割を果たしている事が示唆された。現在MAP2gene targeting用コンストラクトを作成中である。 II)神経細胞の物質輸送における細胞骨格の機能 (1)モーター分子kinesinのモーター領域と微小管との複合体の三次元微細構造の解析。 kinesinの頭部モーター領域をE.coliで精製,微小管と結合させた後,急速凍結,極低温透過型電顕で観察し、三次元の再構成を行い,その微細構造を明らかにした。 (2)新しいモーター分子KIF1A,KIF2,KIF3Bの分子細胞生物学的解析を行った。KIF1Aは単頭順行性モーター(1.5μm/sec)でシナプス小胞の前駆体を運ぶモーターであり,KIF2はホモダイマー順行性モーター(0.4μm/sec)で幼若な神経細胞に多く発現され,シナプス小胞前駆体とは異なる膜小器官を運ぶモーター分子である。KIF3BはKIF3Aとヘテロダイマーを形成し,KAP3と命名した結合蛋白をその尾部に結合させ,順行性(0.4μm/sec)にシナプス小胞前駆体とは異なる膜小器官を輸送するモーター分子である。 (3)kinesinモーター分子のモーター領域に点突然変異を導入しその機能を解析したところ,ライソゾームのゴルジ装置よりの拡散が障害されkinesinがこの機能を担っている事が分かった。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Kanai,Y et al.: "Sorting mechanisms of tau and MAP2 in neurons:suppresed axonal transit of MAP2 and locally regulated microtubule binding." Neuron. 14. 421-432 (1995)
[Publications] Nakagawa,T.et al.: "Two distinct functions of the carboxyl-terminal tail domain of NF-Mupon neurofilament assembly:cross-bridge formation and longitudinal elongation of filaments." Journal of Cell Biology. 129. 411-429 (1995)
[Publications] Noda,Y.et al.: "KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by Kinesin Heavy Chain or KIF3A/B" Jounal of Cell Biology. 129. 157-167 (1995)
[Publications] Okada,Y.et al.: "The activation of protein kinase A pathway selestively inhibits anterograde axonal transport of vesicles but not mitochondria transport or retrograde transport in vivo." Journal of Neuroscience. 15. 3053-3064 (1995)
[Publications] Okada,Y.et al.: "The neuron specific kinesin superfamily protein KIF1A is a unique monomeric motor for the anterograde axonal transport of synaptic vesicle precursors." Cell. 81. 769-780 (1995)
[Publications] Tanaka,Y.et al.: "Identification and molecular evolution of new dynein-like protein sequences in rat brain." Journal of Cell Science. 108. 1883-1893 (1995)
[Publications] Takeda,S.et al.: "Tubulin dynamics in neuronal axons of living zebrafish embryos." Neuron. 14. 1257-1264 (1995)
[Publications] Kikkawa,M.et al.: "Three dimenional structure of the kinesin head-microtubule complex." Nature. 376. 274-276 (1995)
[Publications] Takemura,R.et al.: "Polarity orientation and assembly process of microtubule bundles in nocodazole-treated,MAP2c-transfected COS cells." Molecular Biology of the Cell. 6. 981-996 (1995)
[Publications] Yamazaki,H.et al.: "KIF3A/B:A new heterodimeric kinesin superfamily protein that works as microtubule-plus-end directed motor for fast axonal transport." Journal of Cell Biology. 130. 1387-1399 (1995)
[Publications] Nakata,T.et al.: "Point mutation of ATP-binding motif generated rigor-kinesin which selectively blocks anterograde Iysosome membrane transport." Journal of Cell Biology. 131. 1039-1053 (1995)
[Publications] Takemura,R.et al.: "mRNA expression of KIF1A,KIF2,KIF3A,KIF3B,KIF4,KIF5 and cytoplasmic dynein during axonal regeneration." Journal of Neuroscience. 16. 31-35 (1996)
[Publications] Takei,Y.et al.: "Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system." Journal of Cell Biology. 131. 1789-1800 (1995)

1995 Fiscal Year Annual Research Report

神経細胞・細胞骨格の分子細胞生物学的研究

Principal Investigator

廣川 信隆 東京大学, 医学部(医), 教授 (20010085)

Research Products

[Publications] Kanai,Y et al.: "Sorting mechanisms of tau and MAP2 in neurons:suppresed axonal transit of MAP2 and locally regulated microtubule binding." Neuron. 14. 421-432 (1995)

[Publications] Nakagawa,T.et al.: "Two distinct functions of the carboxyl-terminal tail domain of NF-Mupon neurofilament assembly:cross-bridge formation and longitudinal elongation of filaments." Journal of Cell Biology. 129. 411-429 (1995)

[Publications] Noda,Y.et al.: "KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by Kinesin Heavy Chain or KIF3A/B" Jounal of Cell Biology. 129. 157-167 (1995)

[Publications] Okada,Y.et al.: "The activation of protein kinase A pathway selestively inhibits anterograde axonal transport of vesicles but not mitochondria transport or retrograde transport in vivo." Journal of Neuroscience. 15. 3053-3064 (1995)

[Publications] Okada,Y.et al.: "The neuron specific kinesin superfamily protein KIF1A is a unique monomeric motor for the anterograde axonal transport of synaptic vesicle precursors." Cell. 81. 769-780 (1995)

[Publications] Tanaka,Y.et al.: "Identification and molecular evolution of new dynein-like protein sequences in rat brain." Journal of Cell Science. 108. 1883-1893 (1995)

[Publications] Takeda,S.et al.: "Tubulin dynamics in neuronal axons of living zebrafish embryos." Neuron. 14. 1257-1264 (1995)

[Publications] Kikkawa,M.et al.: "Three dimenional structure of the kinesin head-microtubule complex." Nature. 376. 274-276 (1995)

[Publications] Takemura,R.et al.: "Polarity orientation and assembly process of microtubule bundles in nocodazole-treated,MAP2c-transfected COS cells." Molecular Biology of the Cell. 6. 981-996 (1995)

[Publications] Yamazaki,H.et al.: "KIF3A/B:A new heterodimeric kinesin superfamily protein that works as microtubule-plus-end directed motor for fast axonal transport." Journal of Cell Biology. 130. 1387-1399 (1995)

[Publications] Nakata,T.et al.: "Point mutation of ATP-binding motif generated rigor-kinesin which selectively blocks anterograde Iysosome membrane transport." Journal of Cell Biology. 131. 1039-1053 (1995)

[Publications] Takemura,R.et al.: "mRNA expression of KIF1A,KIF2,KIF3A,KIF3B,KIF4,KIF5 and cytoplasmic dynein during axonal regeneration." Journal of Neuroscience. 16. 31-35 (1996)

[Publications] Takei,Y.et al.: "Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system." Journal of Cell Biology. 131. 1789-1800 (1995)

廣川信隆東京大学, 医学部(医), 教授 (20010085)