Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo.
Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo.
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DOI：
10.1083/jcb.200902153
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发表时间：
2010-04-05
期刊：
影响因子：
--
通讯作者：
Turner JR
中科院分区：
文献类型：
--
作者：
Marchiando AM;Shen L;Graham WV;Weber CR;Schwarz BT;Austin JR 2nd;Raleigh DR;Guan Y;Watson AJ;Montrose MH;Turner JR
尽管肿瘤坏死因子对紧密连接的形态没有明显的影响，但这种促炎细胞因子促进了闭塞素的内化，导致肠内屏障功能的破坏。上皮细胞旁屏障功能主要由紧密连接通透性决定，在疾病中经常被破坏。在肠道中，屏障的丧失可以通过肿瘤坏死因子(α)信号转导和上皮肌球蛋白轻链激酶(MLCK)的激活来实现。然而，肿瘤坏死因子只能引起紧密连接形态的有限改变，结构重组与屏障调节之间的耦合事件还没有定义。我们使用体内成像和表达荧光标记的occludin和ZO-1融合蛋白的转基因小鼠，将occludin内吞作用与肿瘤坏死因子诱导的紧密连接调节联系起来。这种内吞作用需要小窝蛋白-1，对结构和功能的紧密连接调节是必不可少的。这些数据表明，MLCK激活触发了依赖小窝蛋白-1的occludin内吞作用，从而影响结构和功能的紧密连接调节。
Although tight junction morphology is not obviously affected by TNF, this proinflammatory cytokine promotes internalization of occludin, resulting in disrupted barrier function within the intestine. Epithelial paracellular barrier function, determined primarily by tight junction permeability, is frequently disrupted in disease. In the intestine, barrier loss can be mediated by tumor necrosis factor (α) (TNF) signaling and epithelial myosin light chain kinase (MLCK) activation. However, TNF induces only limited alteration of tight junction morphology, and the events that couple structural reorganization to barrier regulation have not been defined. We have used in vivo imaging and transgenic mice expressing fluorescent-tagged occludin and ZO-1 fusion proteins to link occludin endocytosis to TNF-induced tight junction regulation. This endocytosis requires caveolin-1 and is essential for structural and functional tight junction regulation. These data demonstrate that MLCK activation triggers caveolin-1–dependent endocytosis of occludin to effect structural and functional tight junction regulation.
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影响因子：
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作者：
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作者：
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通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
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