Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells.
Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells.
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问号钩端螺旋体在极化的肾近端小管上皮细胞迁移过程中顶端连接复合体的分解。
DOI：
10.1111/cmi.13343
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发表时间：
2021-09
影响因子：
3.4
通讯作者：
Toma C
中科院分区：
文献类型：
--
作者：
Sebastián I;Okura N;Humbel BM;Xu J;Hermawan I;Matsuura C;Hall M;Takayama C;Yamashiro T;Nakamura S;Toma C
细菌病原体已经进化出多种策略来分解上皮细胞顶端连接复合体(AJCs)并感染上皮细胞。钩端螺旋体病是一种广泛流行的人畜共患病，主要由问号钩端螺旋体引起，其跨宿主细胞屏障的传播是其发病的关键。然而，细菌跨越上皮细胞屏障传播的机制仍然缺乏特征性。在这项研究中，我们分析了问号钩端螺旋体与肾近端小管上皮细胞的相互作用，发现在感染后24 小时，问号钩端螺旋体仍以细胞外黏附或爬行的方式与肾近端小管上皮细胞质膜紧密接触。问号钩端螺旋体裂解E-钙粘附素，并通过释放可溶性N-末端片段到细胞外培养上清液诱导其内吞作用。与此同时，跨上皮阻抗(TEER)逐渐降低，AJC蛋白(occludin、claudin-10、ZO-1和cinglin)错位和细胞骨架重排逐渐减少。抑制网状蛋白介导的E-钙粘素内吞作用可阻止TEER的下降。我们发现，上皮细胞中AJCs的分解和细菌通过细胞旁途径的迁移对于问号钩端螺旋体在宿主中的传播是重要的。顶端连接复合体(AJC)由两种类型的细胞间连接(贴壁连接和紧密连接)组成，它们与肌动蛋白细胞骨架相连，形成对上皮细胞屏障重要的黏附网络。问号钩端螺旋体是一种广泛存在的人畜共患病病原体，可引起E-钙粘附素的裂解、内吞、细胞骨架重排和紧密连接蛋白的错位，导致AJC的解体。问号钩端螺旋体附着在细胞连接上，并通过细胞旁途径通过上皮单层进行移行。
Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. In this study, we analysed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 hr post‐infection, L. interrogans remain in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. Leptospira interrogans cleaved E‐cadherin and induced its endocytosis with release of the soluble N‐terminal fragment into the extracellular medium. Concomitantly, a gradual decrease in transepithelial electrical resistance (TEER), mislocalisation of AJC proteins (occludin, claudin‐10, ZO‐1, and cingulin) and cytoskeletal rearrangement were observed. Inhibition of clathrin‐mediated E‐cadherin endocytosis prevented the decrease in TEER. We showed that disassembly of AJCs in epithelial cells and transmigration of bacteria through the paracellular route are important for the dissemination of L. interrogans in the host. The apical junctional complex (AJC) is composed of two types of intercellular junctions (adherens and tight junctions), which are linked to the actin cytoskeleton to create an adhesive network important for the epithelial cell barrier. Leptospira interrogans, a widespread zoonotic pathogen, induces E‐;cadherin cleavage, endocytosis, cytoskeletal rearrangement, and mislocalization of tight junction proteins, resulting in AJC disassembly. L. interrogans attaches to cell junctions and transmigrates through the epithelial monolayer via the paracellular route.
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在瘦素属的HTRA蛋白的硅结构和功能表征中：发病机理的可能影响。
影响因子：
2.9
作者：
Daroz BB;Fernandes LGV;Teixeira AF;Nascimento ALTO
通讯作者：
Nascimento ALTO
影响因子：
5.3
作者：
Aschauer, Lydia;Gruber, Leonhard N.;Jennings, Paul
通讯作者：
Jennings, Paul
影响因子：
5.5
作者：
Koizumi, N;Watanabe, H
通讯作者：
Watanabe, H
DOI：
10.1111/j.1749-6632.2012.06506.x
发表时间：
2012-01-01
期刊：
BARRIERS AND CHANNELS FORMED BY TIGHT JUNCTION PROTEINS I
影响因子：
--
作者：
Citi, Sandra;Pulimeno, Pamela;Paschoud, Serge
通讯作者：
Paschoud, Serge
影响因子：
7.7
作者：
Hoy, Benjamin;Loewer, Martin;Wessler, Silja
通讯作者：
Wessler, Silja