Molecular mechanism of Intracellular Transport: Approaches from molecular Cell Biology, Structural Biology, and Molecular Genetics.

细胞内转运的分子机制：分子细胞生物学、结构生物学和分子遗传学的方法。

基本信息

批准号：
13CE2004
负责人：
HIROKAWA Nobutaka
金额：
$ 1255.04万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for COE Research
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2005
项目状态：
已结题

项目摘要

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

我们涉及使用分子细胞生物学，分子遗传学，生物物理学和结构生物学的细胞内转运阐明后跟随机制的研究。1）鉴定型动蛋白超家族蛋白的所有基因，诸如人类和小鼠等哺乳动物中的KIF。人类遗传神经病。3）KIF2A解聚会使微管的解聚并抑制轴突分支的不必要扩展，因此对大脑接线很重要。4）KIF3将NCADHERIN和β-catenin从Golgi转移到质膜上，并通过抑制beta beta的肿瘤，并抑制肿瘤，并抑制其作用，并将其转移到肿瘤中，并将其转移到cata-catensissis中。 5）KIF3在早期胚胎中的纤毛中转运纤毛中的蛋白质复合物。纤毛通过旋转的轴向后倾斜，从而产生胚外流体的向左淋巴结流动。节点流量…更多地传达了富含脂质的淋巴结囊片，从节点细胞释放出依赖于FGF信号转导向左右和确定左右不对称性的。 KIF3对于重要的身体计划是基础。6）KIF5通过KIF5尾巴和Grip1 -Glur2.7之间的相互作用在树突中运输AMPA型谷氨酸受体受体，KIF5）KIF5还将mRNA与大蛋白复合物一起传递MRNA，KIFC3 KIFC3 KIFC3 kifc3 kifc3 kif5 10）作为向轴突与树突的差分传输机制，我们确定了两种机制。一种是通过识别轴突初始段中的微管的差异，而另一个是通过货物与尾部结构域的结合来控制。 ADP和ATP的原子结构类似KIF2的状态，并阐明了KIF2如何解聚了微管。较少的