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
基本信息
- 批准号:10557011
- 负责人:
- 金额:$ 7.81万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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 analyses 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 barrier without occludin.
封闭蛋白是唯一已知的紧密连接(TJ)的膜整合蛋白,并且现在被认为直接参与TJ的屏障和栅栏功能。封闭蛋白缺陷的胚胎干(ES)细胞产生的封闭蛋白基因的两个等位基因的靶向破坏。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的情况下起屏障作用。
项目成果
期刊论文数量(34)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sonoda,N., Furuse,M., Sasaki,H., Yonemura,S., Kathahira,J., Horiguchi,Y., and Tsukita,Sh.: "Clostridum perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct invokment of claudins in tight juncion barri
Sonoda,N.、Furuse,M.、Sasaki,H.、Yonemura,S.、Kathahira,J.、Horiguchi,Y. 和 Tsukita,Sh.:“产气荚膜梭菌肠毒素片段可从紧密连接链中去除特定的紧密连接蛋白:证据
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- 影响因子:0
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- 通讯作者:
Matsui,T.et al.: "Rho-kinase phosphorylates carboxy-terminal threonines of ERM proteins and regulates their head-to-tail association" J.Cell Biol.140. 647-657 (1998)
Matsui,T.et al.:“Rho 激酶磷酸化 ERM 蛋白的羧基末端苏氨酸并调节它们的头尾关联”J.Cell Biol.140。
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Yonemura S.,Tsukita Sa.and Tsukita Sh.: "Direct involvement of ezrin/radixin/moesin (ERM)-binding membrane proteins in the organization of microvilli in collaboration with activated ERM proteins"J. Cell Biol.. 145. 1497-1506 (1999)
Yonemura S.、Tsukita Sa. 和 Tsukita Sh.:“ezrin/radixin/moesin (ERM) 结合膜蛋白与激活的 ERM 蛋白合作直接参与微绒毛组织”J.
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- 影响因子:0
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- 通讯作者:
Itoh M.,Furuse M.,Morita K.,Kubota K.and Tsukita Sh.: "Molecular basis for the recruitment of three MAGUKs, ZO-1, ZO-2 and ZO-3, to tight junctions: Direct binding of their first PDZ domains to the COOH-termini of claudins"J. Cell Biol.. 147. 1351-1363 (1
Itoh M.、Furuse M.、Morita K.、Kubota K. 和 Tsukita Sh.:“将三种 MAGUK(ZO-1、ZO-2 和 ZO-3)募集至紧密连接的分子基础:它们的直接结合
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- 影响因子:0
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Sonoda N.,Furuse M.,Sasaki H.,Yonemura S.,Katahira J.,Horiguchi Y.and Tsukita Sh.: "Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier"J
Sonoda N.、Furuse M.、Sasaki H.、Yonemura S.、Katahira J.、Horiguchi Y. 和 Tsukita Sh.:“产气荚膜梭菌肠毒素片段从紧密连接链中去除特定的密蛋白:密蛋白直接参与紧密连接的证据
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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:
$ 7.81万 - 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:
$ 7.81万 - 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:
$ 7.81万 - 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:
$ 7.81万 - 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:
$ 7.81万 - 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:
$ 7.81万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
MODULATION OF BLOOD-BRAIN BARRIER
血脑屏障的调节
- 批准号:
06557014 - 财政年份:1994
- 资助金额:
$ 7.81万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
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:
$ 7.81万 - 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:
$ 7.81万 - 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:
$ 7.81万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
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紧密连接分子在遗传性肝内胆汁淤积症发病和病理中的作用分析
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23K06485 - 财政年份:2023
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使用纳米技术定义单通道旁细胞(紧密连接)电导
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10593421 - 财政年份:2023
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The role of tight junction in metastasis of esophageal cancer
紧密连接在食管癌转移中的作用
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镉对血管内皮细胞紧密连接的影响:阐明脱离损伤机制
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