• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

EpCAM蛋白水解及复合紧密连接蛋白7的释放可修复并维持紧密连接屏障。

EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier.

作者信息

Higashi Tomohito, Saito Akira C, Fukazawa Yugo, Furuse Mikio, Higashi Atsuko Y, Ono Masahiro, Chiba Hideki

机构信息

Department of Basic Pathology, Fukushima Medical University, Fukushima, Japan.

Division of Brain Structure and Function, Faculty of Medical Science, Life Science Innovation Center, University of Fukui, Fukui, Japan.

出版信息

J Cell Biol. 2023 Jan 2;222(1). doi: 10.1083/jcb.202204079. Epub 2022 Nov 15.

DOI:10.1083/jcb.202204079
PMID:36378161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9671161/
Abstract

TJs maintain the epithelial barrier by regulating paracellular permeability. Since TJs are under dynamically fluctuating intercellular tension, cells must continuously survey and repair any damage. However, the underlying mechanisms allowing cells to sense TJ damage and repair the barrier are not yet fully understood. Here, we showed that proteinases play an important role in the maintenance of the epithelial barrier. At TJ break sites, EpCAM-claudin-7 complexes on the basolateral membrane become accessible to apical membrane-anchored serine proteinases (MASPs) and the MASPs cleave EpCAM. Biochemical data and imaging analysis suggest that claudin-7 released from EpCAM contributes to the rapid repair of damaged TJs. Knockout (KO) of MASPs drastically reduced barrier function and live-imaging of TJ permeability showed that MASPs-KO cells exhibited increased size, duration, and frequency of leaks. Together, our results reveal a novel mechanism of TJ maintenance through the localized proteolysis of EpCAM at TJ leaks, and provide a better understanding of the dynamic regulation of epithelial permeability.

摘要

紧密连接（TJs）通过调节细胞旁通透性来维持上皮屏障。由于紧密连接处于动态波动的细胞间张力之下，细胞必须持续监测并修复任何损伤。然而，细胞感知紧密连接损伤并修复屏障的潜在机制尚未完全明确。在此，我们表明蛋白酶在上皮屏障的维持中发挥重要作用。在紧密连接断裂位点，基底外侧膜上的EpCAM-闭合蛋白-7复合物可被顶端膜锚定的丝氨酸蛋白酶（MASP）作用，且这些MASP会切割EpCAM。生化数据和成像分析表明，从EpCAM释放的闭合蛋白-7有助于受损紧密连接的快速修复。MASP基因敲除（KO）显著降低了屏障功能，紧密连接通透性的实时成像显示，MASP基因敲除细胞的渗漏大小、持续时间和频率增加。总之，我们的结果揭示了一种通过紧密连接渗漏处EpCAM的局部蛋白水解来维持紧密连接的新机制，并为上皮通透性的动态调节提供了更好的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/740e78e1a97b/JCB_202204079_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/58d1f7cb29eb/JCB_202204079_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/517d4e715175/JCB_202204079_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/0e17c6e502e1/JCB_202204079_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/269f91e5c678/JCB_202204079_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/f28bf74c06da/JCB_202204079_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/9211673ef361/JCB_202204079_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/957234d91c59/JCB_202204079_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/adf0f6ff3945/JCB_202204079_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/ff4c33cd24e0/JCB_202204079_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/c5bbcd6bc773/JCB_202204079_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/c725c6cb1863/JCB_202204079_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/95329d8c8d73/JCB_202204079_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/4ad57c6f66dd/JCB_202204079_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/fbd6da59bfca/JCB_202204079_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/2ed37a2ee617/JCB_202204079_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/740e78e1a97b/JCB_202204079_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/58d1f7cb29eb/JCB_202204079_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/517d4e715175/JCB_202204079_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/0e17c6e502e1/JCB_202204079_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/269f91e5c678/JCB_202204079_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/f28bf74c06da/JCB_202204079_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/9211673ef361/JCB_202204079_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/957234d91c59/JCB_202204079_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/adf0f6ff3945/JCB_202204079_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/ff4c33cd24e0/JCB_202204079_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/c5bbcd6bc773/JCB_202204079_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/c725c6cb1863/JCB_202204079_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/95329d8c8d73/JCB_202204079_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/4ad57c6f66dd/JCB_202204079_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/fbd6da59bfca/JCB_202204079_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/2ed37a2ee617/JCB_202204079_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502a/9671161/740e78e1a97b/JCB_202204079_Fig10.jpg

相似文献

1
EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier.EpCAM蛋白水解及复合紧密连接蛋白7的释放可修复并维持紧密连接屏障。
J Cell Biol. 2023 Jan 2;222(1). doi: 10.1083/jcb.202204079. Epub 2022 Nov 15.
2
Clipping EpCAM to release Claudin-7 for the greater good of the epithelial barrier.剪断 EpCAM 以释放 Claudin-7，造福上皮屏障。
J Cell Biol. 2023 Jan 2;222(1). doi: 10.1083/jcb.202211127. Epub 2022 Dec 14.
3
Epithelial cell adhesion molecule (EpCAM) regulates claudin dynamics and tight junctions.上皮细胞黏附分子（EpCAM）调节紧密连接相关的 Claudin 动态变化。
J Biol Chem. 2013 Apr 26;288(17):12253-68. doi: 10.1074/jbc.M113.457499. Epub 2013 Mar 13.
4
EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins.EpCAM 通过招募 Claudin 蛋白促进肠道上皮细胞中功能性紧密连接的形成。
Dev Biol. 2012 Nov 15;371(2):136-45. doi: 10.1016/j.ydbio.2012.07.005. Epub 2012 Jul 20.
5
Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and fluid homeostasis.敲除小鼠揭示了紧密连接蛋白 18 在肺泡屏障特性和液体动态平衡中的关键作用。
Am J Respir Cell Mol Biol. 2014 Aug;51(2):210-22. doi: 10.1165/rcmb.2013-0353OC.
6
The coculture method to examine interactions between claudin isoforms in tight junction-free HEK293 cells and tight junction-bearing MDCK II cells.用于检测无紧密连接的HEK293细胞和有紧密连接的MDCK II细胞中claudin亚型之间相互作用的共培养方法。
Methods Mol Biol. 2011;762:101-14. doi: 10.1007/978-1-61779-185-7_8.
7
Reconstitution of functional tight junctions with individual claudin subtypes in epithelial cells.上皮细胞中用单个闭合蛋白亚型重建功能性紧密连接。
Cell Struct Funct. 2023 Jan 20;48(1):1-17. doi: 10.1247/csf.22068. Epub 2022 Dec 9.
8
The Claudins: From Tight Junctions to Biological Systems.紧密连接蛋白 Claudin：从紧密连接到生物系统。
Trends Biochem Sci. 2019 Feb;44(2):141-152. doi: 10.1016/j.tibs.2018.09.008. Epub 2018 Oct 25.
9
AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability.AP2M1 通过内吞作用和与 LC3 的相互作用介导自噬诱导的 CLDN2（紧密连接蛋白 2）降解，从而降低肠道上皮细胞紧密连接的通透性。
Autophagy. 2022 Sep;18(9):2086-2103. doi: 10.1080/15548627.2021.2016233. Epub 2021 Dec 29.
10
Model for the architecture of claudin-based paracellular ion channels through tight junctions.基于紧密连接的 Claudin 型细胞旁离子通道的结构模型。
J Mol Biol. 2015 Jan 30;427(2):291-7. doi: 10.1016/j.jmb.2014.10.020. Epub 2014 Nov 4.

引用本文的文献

1
Rho-ROCK liberates sequestered claudin for rapid de novo tight junction formation.Rho-ROCK释放被隔离的紧密连接蛋白，以快速重新形成紧密连接。
Elife. 2025 Jul 24;13:RP102794. doi: 10.7554/eLife.102794.
2
Molecular determinants of neuroprotection in blood-brain interfaces of the cynomolgus monkey.食蟹猴血脑界面神经保护的分子决定因素
Front Pharmacol. 2025 Mar 12;16:1523819. doi: 10.3389/fphar.2025.1523819. eCollection 2025.
3
Molecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan.

本文引用的文献

1
Effects of TAMP family on the tight junction strand network and barrier function in epithelial cells.TAMP家族对上皮细胞紧密连接链网络和屏障功能的影响。
Ann N Y Acad Sci. 2022 Nov;1517(1):234-250. doi: 10.1111/nyas.14889. Epub 2022 Sep 7.
2
Nanoscale segregation of channel and barrier claudins enables paracellular ion flux.纳米尺度上的通道和屏障紧密连接蛋白的分隔使细胞旁离子通量成为可能。
Nat Commun. 2022 Aug 25;13(1):4985. doi: 10.1038/s41467-022-32533-4.
3
Tight junction channel regulation by interclaudin interference. Claudin 干扰调节紧密连接通道。
细胞外基质受体 dystroglycan 的蛋白水解切割调控的分子基础。
Structure. 2024 Nov 7;32(11):1984-1996.e5. doi: 10.1016/j.str.2024.08.019. Epub 2024 Sep 20.
4
Loss of intermicrovillar adhesion factor CDHR2 impairs basolateral junctional complexes in transporting epithelia.细胞间微绒毛黏附因子 CDHR2 的缺失会破坏转运上皮细胞的基底外侧连接复合体。
Mol Biol Cell. 2024 Nov 1;35(11):br21. doi: 10.1091/mbc.E24-03-0113. Epub 2024 Sep 18.
5
Regulation of the Function and Expression of EpCAM.上皮细胞黏附分子（EpCAM）功能与表达的调控
Biomedicines. 2024 May 20;12(5):1129. doi: 10.3390/biomedicines12051129.
6
Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex.紧密连接膜蛋白调节顶端连接复合体的机械阻力。
J Cell Biol. 2024 May 6;223(5). doi: 10.1083/jcb.202307104. Epub 2024 Mar 22.
7
ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism detecting alteration of septate junction integrity in epithelial cells.ESCRT-III 依赖性的黏附和机械变化是由一种机制触发的，该机制可以检测到上皮细胞中隔膜连接完整性的改变。
Elife. 2024 Feb 2;13:e91246. doi: 10.7554/eLife.91246.
8
Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport.Tmprss2 维持上皮屏障完整性和跨上皮钠转运。
Life Sci Alliance. 2024 Jan 3;7(3). doi: 10.26508/lsa.202302304. Print 2024 Mar.
9
Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity.肾脏特异性膜结合丝氨酸蛋白酶 CAP1/Prss8 和 CAP3/St14 影响 ENaC 亚基的丰度但不影响其活性。
Cells. 2023 Sep 23;12(19):2342. doi: 10.3390/cells12192342.
10
Early-onset tufting enteropathy in HAI-2-deficient mice is independent of matriptase-mediated cleavage of EpCAM.HAI-2 缺陷型小鼠的早发型丛状线-肠病与 EpCAM 的 matriptase 介导的裂解无关。
Development. 2023 Sep 1;150(17). doi: 10.1242/dev.201801. Epub 2023 Aug 31.
Nat Commun. 2022 Jun 30;13(1):3780. doi: 10.1038/s41467-022-31587-8.
4
EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.EPCAM 和 TROP2 在 Claudin 稳定和肠道及肠外上皮细胞的发育中发挥作用。
Biol Open. 2022 Jul 15;11(7). doi: 10.1242/bio.059403. Epub 2022 Jul 11.
5
Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling.机械敏感性钙闪光促进紧密连接重塑过程中 RhoA 的持续激活。
J Cell Biol. 2022 Apr 4;221(4). doi: 10.1083/jcb.202105107. Epub 2022 Mar 7.
6
Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
7
Variants of human CLDN9 cause mild to profound hearing loss.人类 CLDN9 的变异导致轻度至重度听力损失。
Hum Mutat. 2021 Oct;42(10):1321-1335. doi: 10.1002/humu.24260. Epub 2021 Aug 1.
8
EpCAM promotes endosomal modulation of the cortical RhoA zone for epithelial organization.EpCAM 促进皮质 RhoA 区的内体调节，以维持上皮组织的形态。
Nat Commun. 2021 Apr 13;12(1):2226. doi: 10.1038/s41467-021-22482-9.
9
Sealing holes in cellular membranes.封闭细胞膜上的孔洞。
EMBO J. 2021 Apr 1;40(7):e106922. doi: 10.15252/embj.2020106922. Epub 2021 Mar 1.
10
Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function.紧密连接嵴网络的吻合需要封闭蛋白和三角蛋白形成，从而改善屏障功能。
Mol Biol Cell. 2021 Apr 15;32(8):722-738. doi: 10.1091/mbc.E20-07-0464. Epub 2021 Feb 10.