Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function.
Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function.
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DOI：
10.1038/s41467-023-41999-9
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发表时间：
2023-10-05
影响因子：
16.6
通讯作者：
Nusrat, Asma
中科院分区：
文献类型：
--
作者：
Raya-Sandino, Arturo;Lozada-Soto, Kristen M.;Rajagopal, Nandhini;Garcia-Hernandez, Vicky;Luissint, Anny-Claude;Brazil, Jennifer C.;Cui, Guiying;Koval, Michael;Parkos, Charles A.;Nangia, Shikha;Nusrat, Asma
紧密连接蛋白家族紧密连接蛋白形成调节上皮屏障功能的电荷和大小选择性细胞旁通道。在胃肠道中，屏障异质性归因于不同的claudin表达。在这里，我们表明，claudin-23（CLDN 23）是丰富的管腔肠上皮细胞，它加强了上皮屏障。互补方法揭示，CLDN 23通过与CLDN 3和CLDN 4缔合并调节它们在紧密连接中的分布来调节细胞旁离子和大分子渗透性。计算建模表明，CLDN 23与CLDN 3和CLDN 4形成具有独特孔结构和总净电荷的异聚和异型复合物。这些计算模拟分析进一步表明，孔特性是相互作用依赖的，因为具有相同的密蛋白化学计量的不同组织的复合物形成具有独特结构的孔。我们的研究结果提供了对紧密连接组织的深入了解，并提出了一个模型，即不同的claudin联合收割机结合形成多种不同的复合物，通过改变紧密连接结构来改变上皮屏障功能。紧密连接蛋白家族蛋白对于调节上皮屏障功能是重要的。在这里，作者表明，claudin-23通过与其他claudin结合来改变紧密连接结构和渗透性，从而控制细胞旁流量。
Claudin family tight junction proteins form charge- and size-selective paracellular channels that regulate epithelial barrier function. In the gastrointestinal tract, barrier heterogeneity is attributed to differential claudin expression. Here, we show that claudin-23 (CLDN23) is enriched in luminal intestinal epithelial cells where it strengthens the epithelial barrier. Complementary approaches reveal that CLDN23 regulates paracellular ion and macromolecule permeability by associating with CLDN3 and CLDN4 and regulating their distribution in tight junctions. Computational modeling suggests that CLDN23 forms heteromeric and heterotypic complexes with CLDN3 and CLDN4 that have unique pore architecture and overall net charge. These computational simulation analyses further suggest that pore properties are interaction-dependent, since differently organized complexes with the same claudin stoichiometry form pores with unique architecture. Our findings provide insight into tight junction organization and propose a model whereby different claudins combine to form multiple distinct complexes that modify epithelial barrier function by altering tight junction structure. Claudin family proteins are important for regulating epithelial barrier function. Here the authors show that claudin-23 controls paracellular flux by combining with other claudins to alter tight junction architecture and permeability.
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影响因子：
3.3
作者：
Alberini, Giulio;Benfenati, Fabio;Maragliano, Luca
通讯作者：
Maragliano, Luca
影响因子：
5.5
作者：
Colegio, OR;Van Itallie, C;Anderson, JM
通讯作者：
Anderson, JM
影响因子：
2.4
作者：
CLAUDE, P
通讯作者：
CLAUDE, P
DOI：
10.1152/ajplung.00182.2003
发表时间：
2003-11-01
影响因子：
4.9
作者：
Coyne, CB;Gambling, TM;Johnson, LG
通讯作者：
Johnson, LG
影响因子：
8
作者：
Flemming, Sven;Luissint, Anny-Claude;Parkos, Charles A.
通讯作者：
Parkos, Charles A.