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
基本信息
- 批准号:11307002
- 负责人:
- 金额:$ 24.12万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
(1) The tight junction (TJ) and its adhesion molecules, claudins, are responsible for the barrier function of simple epithelia, but TJs have not been thought to play an important role in the barrier function of mammalian stratified epithelia including the epidermis. In this study, we generated claudin-1-deficient mice and found that the animals died within one day of birth with wrinkled skin. Dehydration assay as well as transepidermal water loss measurements revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal. These unexpected findings prompted us to re-examine TJs in the epidermis of wild-type mice. Close inspection by immunofluorescence microscopy with an anti-occludin mAb, a Tjspecific marker, identified continuous TJs in the stratum granulosum, where claudin-1 and -4 were concentrated. In claudin-1-deficient mice, claudin-1 appeared to have simply been removed from these TJs leaving occlu … More din(and also claudin-4)-positive TJs. Interestingly, in the wild-type epidermis, these occludin-positive TJs efficiently prevented the diffusion of subcutaneously-injected tracer (〜600 dalton) toward the skin surface, whereas in the claudin-1-deficient epidermis, the tracer appeared to pass through these TJs. These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis, and that these TJs are crusial for the barrier function of the mammalian skin.(2) The tight junction (TJ) stand is linear polymer, typical of proteinaceous polymers within plasma membranes, the physicochemical nature of which remains elusive. Recently, claudins were identified as major constituents of TJ strands, and they were shown to reconstitute TJ strands at cell-cell borders when exogenously expressed in mouse L fibroblasts. In this study, we show that the GFP (green fluorescent protein) fusion protein with claudin-1 can also reconstitute TJ strands in L fibroblasts, allowing us to directly observe individual TJ strands in live cells. Less
(1)紧密连接(TJ)及其粘附分子claudins负责简单上皮的屏障功能,但TJ在哺乳动物复层上皮(包括表皮)的屏障功能中并不重要。在这项研究中,我们产生了claudin-1缺陷小鼠,发现这些动物在出生后一天内死亡,皮肤起皱。脱水测定以及经表皮水分损失测量显示,在这些小鼠中,表皮屏障受到严重影响,尽管角质形成细胞的分层组织似乎是正常的。这些意想不到的发现促使我们重新检查野生型小鼠表皮中的TJ。通过免疫荧光显微镜用抗闭合蛋白mAb(一种TJ特异性标记物)仔细检查,鉴定了颗粒层中的连续TJ,其中紧密连接蛋白-1和-4被浓缩。在claudin-1缺陷的小鼠中,claudin-1似乎只是从这些TJ中去除, ...更多信息 din(以及claudin-4)阳性TJ。有趣的是,在野生型表皮中,这些闭合蛋白阳性TJ有效地防止皮下注射的示踪剂(10600道尔顿)向皮肤表面扩散,而在闭合蛋白-1缺陷型表皮中,示踪剂似乎穿过这些TJ。这些发现提供了第一个证据,即连续的基于密蛋白的TJ发生在表皮中,并且这些TJ对于哺乳动物皮肤的屏障功能是至关重要的。(2)紧密连接(TJ)是线性聚合物,是质膜内典型的蛋白质聚合物,其物理化学性质仍然难以捉摸。最近,claudins被确定为TJ链的主要成分,并且当在小鼠L成纤维细胞中外源表达时,它们显示出在细胞-细胞边界处重建TJ链。在这项研究中,我们表明,GFP(绿色荧光蛋白)融合蛋白与claudin-1也可以重建TJ链在L成纤维细胞,使我们能够直接观察活细胞中的个别TJ链。少
项目成果
期刊论文数量(31)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
三森,清末優子: "Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells"Journal of Cell Biology. 148. 505-518 (2000)
Mimori、Yuko Kiyosue:“腺瘤性息肉病大肠杆菌 (APC) 蛋白沿着微管移动并集中在上皮细胞的生长末端”,《细胞生物学杂志》148. 505-518 (2000)。
- DOI:
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- 影响因子:0
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Furuse M., Sasaki H., Tsukita Sh.: "Manner of interaction of heterogenous claudin species within and between tight junction strands"J.Cell Biol.. 147. 891-903 (1999)
Furuse M.、Sasaki H.、Tsukita Sh.:“紧密连接链内和之间异源密蛋白种类的相互作用方式”J.Cell Biol.. 147. 891-903 (1999)
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Tsukita S.: "Melti-fomcfional strands in fight junetions"Nature Review of Melecular Cell Biology. 2. 285-293 (2001)
Tsukita S.:“战斗连接中的熔化链”《分子细胞生物学自然评论》。
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- 影响因子:0
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Morita, K., Sasaki, H., Furuse, M.and Tsukita, Sh.: "Endothelial claudin : claudin-5/TMVCF constitutes tight junction strands in endothelial cells."J.Cell Biol.. 147. 185-194 (1999)
Morita, K.、Sasaki, H.、Furuse, M. 和 Tsukita, Sh.:“内皮紧密蛋白:claudin-5/TMVCF 构成内皮细胞中的紧密连接链。”J.Cell Biol.. 147. 185-194 (
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Morita K., Sasaki H., Fujimoto K., Furuse M., Tsukita Sh.: "Claudin-11/OSP-based tight junctions in myelinated sheaths of oligodendrocytes and in Sertoli cells in testis"J.Cell Biol.. 145. 579-588 (1999)
Morita K.、Sasaki H.、Fujimoto K.、Furuse M.、Tsukita Sh.:“少突胶质细胞有髓鞘和睾丸支持细胞中基于 Claudin-11/OSP 的紧密连接”J.Cell Biol.. 145。
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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:
$ 24.12万 - 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:
$ 24.12万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 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:
$ 24.12万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
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