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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 Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Research InstitutionThe 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 (田中 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)
岡部 繁男  東京大学, 医学部, 助手 (60204012)
依藤 宏  東京大学, 医学部, 講師 (00158544)
Project Period (FY) 1992 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥300,000,000 (Direct Cost: ¥300,000,000)
Fiscal Year 1995: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1994: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 1993: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 1992: ¥130,000,000 (Direct Cost: ¥130,000,000)
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 / 細胞骨格 / 分子細胞生物学 / 細胞の形態形成 / 物質輸送 / 微小管結合性モーター分子 / KIFs / 形態形成 / タウ / MAP2 / MAP2C / Tau / 新しいモータ 分子
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。

Report

(4 results)
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (61 results)

All Other

All Publications (61 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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

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

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

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [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)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirokawa,N.: "Microtubule organization and dynaics on Microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-83 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] Harada,A.et al.: "Altered microtubule orgnization in small-calibro xons of mice lacking tau protein" Nature. 36. 488-491 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] TAkeda,S.et al.: "DIfferential dynamics of neurofilament H protein and neurofilament I,protein in neuron" Journal of Cell Biology. 127. 173-186 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nangaku,M.et al.: "KIF1B;Anew microtubule plus-end directed monomeric for mitochondria transport" Cell. 39. 1209-1220 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] 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)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takemura,R.: "Reorganization of brain spectrin(fodrin)during differentiation of PC12 cells." Neuroscience. 52. 381-391 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Umeyama,T.: "Dynamics of microtubules bundled by microtubule associated protein 2 C(MAP2)." Journal of Cell Biology. 120. 451-465 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okabe,S.: "Do photobleached fluorescent microtubules move ?:Reevaluation of fluorescence laser photobleaching both in vitro and in growing Xenopus axon." Journal of Cell Biology. 120. 1177-1186 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okabe,S.: "Dynamics of the neuronal intermediate filaments." Journal of Cell Biology. 121. 375-386 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakata,T.: "A novel member of dynamin-family of GTP-binding protein is expressed specifically to testis." Journal of Cell Science. 105. 1-5 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Noda,Y.: "Localization of dynamin:Widespread distribution in neurons and association with membraneous organelles transported anterogradely." Neuroscience. 55. 113-127 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Zhang,Z.: "The primary structure of rat brain dynein heavy chain,a cytoplasmic motor enzyme." Proceeding of the National Academy of Science of the USA. 90. 7928-7932 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirokawa,N.: "Axonal transport and the cytoskeleton." Current Opinion in Neurobiology.3. 724-731 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirokawa,N.: "Mechanism of axonal transport.Identification of new molecular motors and regulations of transports." Neuroscience Research. 18. 1-9 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Miyasaka,H.: "Interaction of the tail domain of high molecular weight subunits of neurofilaments with the C-terminal region of tubulin and its regulation by tau protein kinase II." Journal of Biological Chemistry. 268. 22695-22702 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakata,T.: "Thermal Drift is enough to drive microtubules in the absense of motor proteins." Biophysical Journal. 65. 2504-2510 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirokawa,N.: "Microtubule organization and dynamics dependent on microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-82 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Harada,A.: "Tau is not essential for polarized neuronal cell morphogenesis but important for microtubule organization and stabilization in small caliber axons." Nature. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hagiwara,H.: "Interaction between cytoplasmic dynein and tau or MAP2 for the binding to microtubules." Journal of Biological Chemistry. 269. 3581-3589 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeuchi,M.: "The 72KD microtubule associated protein form porcine brain." Journal of Neurochemistry. 58. 1510-1516 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okabe,S.: "Differential behavior of photoactivated microtubules in growing axon of mouse and frog neurons." Journal of Cell Biology. 117. 105-120 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hirokawa,N.: "Microtubules on the move ?" Current Biology. 2. 193-195 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakata,T.: "Ordanization of cortical cytoskeleton of cultured chromaff in cells and involvement in secretion as revealed by quick-freeze,deep-etchig,and double-label immunoelectrom microscopy." Journal of Neuroscience. 12. 2186-2197 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oshima,T.: "Immunocytochemical localization of 205 kDa microtubule-associated protein (205kDa MAP) in the guinea pig organ of corti." Brain Research. 590. 53-65 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Maeda,K.: "Dynamin:its enzymatic activity and interaction with microtubules." Molecular Biology of the Cell. 3. 1181-1194 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takemura,R.: "Reorganization of brain spectrin (fodrin) during differentiation of PC12 cells." Neuroscience. 52. 381-391 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Umeyama,T.: "Dynamics of microtubules bundled by microtubule associated protein 2 C (MAP2)." Journal of Cell Biology. 120. 451-465 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okabe,S.: "Do photobleached fluorescent microtubules move ? Re-evaluation of fluorescence laser photobleaching both in vitro and in growing Xenopus axon." Journal of Cell Biology. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Noda,Y.: "Localization association with membraneous organelles transported of dynamin:Widespread distribution in neurons and anterogradely." Neuroscience. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okabe,S.: "Dynamics of the neuronal intermediate filaments." Journal of Cell. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakata,T.: "T-dynamin,a novel member of dynamin-family protein is expressed specific to testis." Journal of Cell Science. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kanai,Y.: "Microtubule bundling by tau proteins in vivo:analysis of the functional domains." EMBO Journal. 11. 3953-3961 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Aizawa,H.: "Kinesin family in murine central nervous system." Journal of Cell Biology. 119. 1287-1296 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tanaka,Y.: "Chronological expression of microtubule-associated proteins (MAPs) in EC cell p 19 after neuronal inductin by retinoic acid." Brain Research. 596. 269-278 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sato-Yoshitake: "Phosphorylation of kinesin reguiates its binding to synaptic vesicles." Journal of Biological Chemistry. 267. 23930-23936 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Chen,J.: "Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons." Nature. 360. 674-677 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takemura,R.: "Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B,MAP2 or tau." Journal of Cell Science. 103. 953-964 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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