2005 Fiscal Year Final Research Report Summary
Molecular mechanism of Intracellular Transport: Approaches from molecular Cell Biology, Structural Biology, and Molecular Genetics.
| Project/Area Number |
13CE2004
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| Research Category |
Grant-in-Aid for COE Research
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIROKAWA Nobutaka The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20010085)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Takao The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50218004)
NODA Yasuko The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (50262019)
KANAI Yoshimitsu The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80214427)
TANAKA Yosuke The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (90302661)
TAKEI Yosuke The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20272487)
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| Project Period (FY) |
2001 – 2005
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| Keywords | molecular motors / kinesin / microtubules / intracellular transport / molecular cell biology / molecular genetics / structural biology |
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| Research Abstract |
Our research concerning the mechanism of intracellular transport elucidated followings using molecular cell biology, molecular genetics, biophysics and structural biology.
1) Identification of all genes of kinesin superfamily proteins, KIFs in mammals such as human and mouse.
2) KIF1B beta transport synaptic vesicle precursor and fundamental for neuronal function and survival and it is a responsible gene of a human hereditary neuropathy.
3) KIF2A depolymerizes microtubules and suppress unnecessary extension of axonal branches thus important for brain wiring.
4) KIF3 transports Ncadherin and beta-catenin from Golgi to plasma membrane and suppresses tumorigenesis by suppressing beta-catenins transfer into the nucleus and its function as a transcriptional factor for cell proliferation.
5) KIF3 transports protein complexes in the cilia at the ventral node in early embryo. The cilia generate leftward nodal flow of extraembryonic fluid by rotation whose axis is tilted posteriorly. The nodal flow
… More
convey lipid-enriched nodal vesicular parcels released from node cells dependent on FGF signaling toward left and determine left-right asymmetry. Thus KIF3 is fundamental for important body planning.
6) KIF5 transport AMPA type glutamate receptors in dendrites through the interaction between KIF5 tail and GRIP1 - GluR2.
7) KIF5 also transport mRNAs with a large protein complexes related to RNAs in dendrites.
8) KIF17 transport NMDA type glutamate receptors in dendrites through interaction between KI17tail and scaffolding protein complexes and this transport is shown to be important for higher brain function such as working and special memories.
9) KIFC3 transports vesicles containing Anexin XIIIb to the apical membrane of epitherial cells, and plays a role in localization and integrity of the Golgi apparatus.
10) As mechanisms for differential transport to axon vs dendrites we identified two mechanism. One is by the recognition of the difference of microtubules in the axon initial segment by motor domain and other is by control via binding of cargoes to the tail domain.
11) We revealed that motor protein can move processively along microtubules as monomer by biased Brownian movement and also solved atomic structure of KIF1A motor domain of 5 different states during ATP hydrolysis, thus how conformational changes occur in the motor domain.
12) We solved atomic structures of ADP and ATP like states of KIF2 and elucidated how KIF2 depolymerizes microtubules. Less
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[Journal Article] Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta.2001
Author(s)
Zhao, C., J.Takita, Y.Tanaka, M.Setou, T.Nakagawa, S.Takeda, H.W.Yang, S.Terada, T.Nakata, Y.Takei, M.Saito, S.Tsuji, Y.Hayashi, N.Hirokawa.
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Journal Title
Cell 105(5)
Pages: 587-597
Description
「研究成果報告書概要(欧文)」より
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