MODULATION OF BLOOD-BRAIN BARRIER

血脑屏障的调节

基本信息

项目摘要

To modulate the blood-brain barrier, i.e.tight junctions, we analyzed the functions of occludin. Occludin is the only known integral membrane protein of tight junctions (TJ), and is now believed to be directly involved in the barrier and fence functions of TJ.Occludin-deficient embryonic stem (ES) cells were generated by targeted disruption of both alleles of the occludin gene. When these cells were subjected to suspension culture, they aggregated to form simple, and then cystic embryoid bodies (EBs) with the same time course as EB formation from wild-type ES cells. Immunofluorescence microscopy and ultrathin section electron microscopy revealed that polarized epithelial (visceral endoderm-like) cells were differentiated to delineate EBs not only from wild-type but also from occludin-deficient ES cells. Freeze fracture analyzes indicated no significant differences in number or morphology of TJ strands between wild-type and occludin-deficient epithelial cells. Furthermore, ZO-1, a TJ-associated peripheral membrane protein, was still exclusively concentrated at TJ in occludin-deficient epithelial cells. In good agreement with these morphological observations, TJ in occludin-deficient epithelial cells functioned as a primary barrier to the diffusion of a low molecular mass tracer through the paracellular pathway. These findings indicate that there are as yet unidentified TJ integral membrane protein(s) which can form strand structures, recruit ZO-1, and function as a barrier without occludin.
为了调节血脑屏障,即紧密连接,我们分析了闭合蛋白的功能。封闭蛋白是紧密连接(TJ)中唯一已知的膜蛋白,与TJ的屏障和栅栏功能密切相关。封闭蛋白缺陷型胚胎干细胞(ES)是通过靶向破坏封闭蛋白基因的两个等位基因而产生的。当这些细胞进行悬浮培养时,它们聚集形成简单的,然后是囊性胚状体(EB),其时间过程与野生型ES细胞形成EB的时间过程相同。免疫荧光显微镜和透射电镜显示,极化上皮(内脏内胚层样)细胞分化描绘EB不仅从野生型,但也从occludin缺陷的ES细胞。冷冻断裂分析表明,野生型和闭合蛋白缺陷的上皮细胞之间的TJ链的数量或形态没有显着差异。此外,ZO-1,TJ相关的外周膜蛋白,仍然只集中在TJ在闭塞素缺陷的上皮细胞。在良好的协议与这些形态学观察,TJ在闭塞素缺陷的上皮细胞作为一个主要的障碍,低分子量示踪剂通过细胞旁途径的扩散。这些发现表明,存在尚未鉴定的TJ整合膜蛋白,其可以形成链结构,募集ZO-1,并且在没有occludin的情况下作为屏障起作用。

项目成果

期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nagafuchi, A., Ishihara, S., and Tsukita, Sh.: "The roles of catenins in the cadherin-mediated cell adhesion : Functional analysis of E-cadherin alpha catenin fusion molecules." J.Cell Biol.127. 235-245 (1994)
Nagafuchi, A.、Ishihara, S. 和 Tsukita, Sh.:“连环蛋白在钙粘蛋白介导的细胞粘附中的作用:E-钙粘蛋白 α 连环蛋白融合分子的功能分析。”
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Hirase, T., Furuse, M., Tsukita, Sh: "A 155kDa undercoat-constitutive protein of cell-to-cell adherens junctions" Eur.J.Cell Biol.72. 174-181 (1997)
Hirase, T.、Furuse, M.、Tsukita, Sh:“细胞间粘附连接的 155kDa 底层组成蛋白”Eur.J.Cell Biol.72。
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Takeuchi,K.: "Structural diversity of band 4.1 superfamily members." J.Coll Sci. 107. 1921-1928 (1994)
Takeuchi,K.:“带 4.1 超家族成员的结构多样性。”
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Nagafuchi,A.: "The roles of catenins in the cadherin-mediated cell adhesion:Functional analysis of E-cadherin-alpha catenin fusion molecules." J.Cell Biol. 127. 602-613 (1994)
Nagafuchi,A.:“连环蛋白在钙粘蛋白介导的细胞粘附中的作用:E-钙粘蛋白-α连环蛋白融合分子的功能分析。”
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Takeda, H., Nagafuchi, A., Yonemura, S., Tsukita, Sa.: "V-src kinase shifts the cadherin-based cell adhesion from the strong to the weak state and beta-catenin is not required for the shift." J.Cell Biol.131. 1839-1847 (1995)
Takeda, H.、Nagafuchi, A.、Yonemura, S.、Tsukita, Sa.:“V-src 激酶将基于钙粘蛋白的细胞粘附从强状态转变为弱状态,并且这种转变不需要 β-连环蛋白。
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TSUKITA Shoichiro其他文献

TSUKITA Shoichiro的其他文献

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{{ truncateString('TSUKITA Shoichiro', 18)}}的其他基金

Claudins in the epithelium/endothelium barrier dysfucrition
上皮/内皮屏障功能障碍中的 Claudins
  • 批准号:
    14207008
  • 财政年份:
    2002
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Molecular mechanism for cell-cell adhesion in canceration and metastasis
癌变和转移中细胞粘附的分子机制
  • 批准号:
    12219210
  • 财政年份:
    2000
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
The claudin family : Its involvement in interecellular sealing and epithelial polarity
密蛋白家族:参与细胞间密封和上皮极性
  • 批准号:
    11307002
  • 财政年份:
    1999
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
CLAUDINS AND OCCLUDIN : COMPARISON WITH CONNEXIN
CLAUDINS 和 OCCLUDIN:与 CONNEXIN 的比较
  • 批准号:
    11694270
  • 财政年份:
    1999
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Development of a new drug delivery method by the use of occludin molecules
利用occludin分子开发新的药物递送方法
  • 批准号:
    10557011
  • 财政年份:
    1998
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Structure and function of occludin in tight junctions : comparison with connexin gap junctions
紧密连接中occludin的结构和功能:与连接蛋白间隙连接的比较
  • 批准号:
    09044290
  • 财政年份:
    1997
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
The structure and functions of occludin
occludin的结构和功能
  • 批准号:
    08407006
  • 财政年份:
    1996
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
CELL ADHESION-DEPENDENT REGULATION OF CELL GROWTH AND DIFFERENTIATION
细胞生长和分化的细胞粘附依赖性调节
  • 批准号:
    06404083
  • 财政年份:
    1994
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (A)
Time-lapse Electron Microscopy with Caged Compounds
笼状化合物的延时电子显微镜
  • 批准号:
    04558034
  • 财政年份:
    1992
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
A New Rapid Freezing Apparatus for Electron Microscopy
一种新型电子显微镜快速冷冻装置
  • 批准号:
    02558026
  • 财政年份:
    1990
  • 资助金额:
    $ 8万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)

相似海外基金

The regulation of tight junction function via disulfide bond formation as a redox signaling
通过二硫键形成作为氧化还原信号调节紧密连接功能
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    2017
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Mechanisms of Cytoskeletal Regulation of Tight Junction Homeostasis and Repair
细胞骨架对紧密连接稳态和修复的调节机制
  • 批准号:
    9206081
  • 财政年份:
    2015
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Mechanisms of Cytoskeletal Regulation of Tight Junction Homeostasis and Repair
细胞骨架对紧密连接稳态和修复的调节机制
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Role of the chloride channel ClC-2 in intestinal tight junction barrier recovery
氯离子通道 ClC-2 在肠道紧密连接屏障恢复中的作用
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Mechanisms of tight junction pore and leak pathway regulation in intestinal mucos
肠粘膜紧密连接孔和渗漏途径的调节机制
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    8881173
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氯离子通道 ClC-2 在肠道紧密连接屏障恢复中的作用
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Role of the chloride channel ClC-2 in intestinal tight junction barrier recovery
氯离子通道 ClC-2 在肠道紧密连接屏障恢复中的作用
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