Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy.
Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy.
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DOI：
10.1111/nyas.14855
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发表时间：
2022-10
影响因子：
5.2
通讯作者：
Chen YH
中科院分区：
文献类型：
--
作者：
Naser AN;Guiler W;Lu Q;Chen YH
上皮细胞通过定义的顶端紧密连接（TJ）、侧向粘附连接（AJs）和基底整合素-基质相互作用极化。然而，越来越多的人认识到，居民细胞连接蛋白可以在不同的位置和以前未认识到的功能。我们的研究在这里提出了纳米结构和纳米共定位的细胞连接蛋白在培养和组织中的随机光学重建显微镜（STORM）。非癌性MDCK-II和PZ-HPV-7细胞-细胞连接的Z轴视图解析了β-连环蛋白和p120 ctn定位于TJ和AJs，其中p120 ctn位于β-连环蛋白顶端并与TJ蛋白claudin-7共定位。更基本的是，p120 ctn和β-catenin变得共定位。这种拓扑结构在同基因Ras转化的MDCK细胞和癌性PC 3细胞中丢失，其中p120 ctn相对于β-连环蛋白变得基底定位。Claudin-7基因条件性敲除（cKO）小鼠中p120 ctn相对于β-catenin的极性也发生了改变，就像在正常细胞向癌细胞表型转化中所看到的那样。此外，claudin-7 cKO导致其他细胞连接蛋白的重新分布和重新定位，包括claudin-1、闭锁小带-1、整合素α2、上皮细胞粘附分子和粘着斑激酶（FAK）;具体而言，在顶侧室观察到整合素α2和FAK。我们的数据表明，STORM揭示了以前未表征的区域细胞连接纳米结构，为蛋白质功能的潜在跨室调节提供了新的见解。我们的数据表明，随机光学重建显微镜揭示了以前未表征的区域细胞连接纳米结构，为蛋白质功能的潜在跨室调节提供了新的见解。
Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin–matrix interactions. However, it is increasingly recognized that resident cell junction proteins can be found in varying locations and with previously unrecognized functions. Our study here presents the nanoarchitecture and nanocolocalization of cell junction proteins in culture and tissue by stochastic optical reconstruction microscopy (STORM). The Z‐axial view of noncancerous MDCK‐II and PZ‐HPV‐7 cell–cell junctions resolved β‐catenin and p120ctn localizations to TJs and AJs, with p120ctn apical to β‐catenin and colocalizing with TJ protein claudin‐7. More basally, p120ctn and β‐catenin become colocalized. This topography was lost in isogenic Ras‐transformed MDCK cells and cancerous PC3 cells, where p120ctn becomes basally localized in relation to β‐catenin. Claudin‐7 gene conditional knockout (cKO) in mice also have altered polarity of p120ctn relative to β‐catenin, like that seen in normal‐to‐cancer cell phenotypic transformation. Additionally, claudin‐7 cKO resulted in redistribution and relocalization of other cell junction proteins, including claudin‐1, zonula occludens‐1, integrin α2, epithelial cell adhesion molecule, and focal adhesion kinase (FAK); specifically, integrin α2 and FAK were observed at the apical–lateral compartment. Our data show that STORM reveals regional cellular junction nanoarchitecture previously uncharacterized, providing new insight into potential trans‐compartmental modulation of protein functions. Our data show that stochastic optical reconstruction microscopy reveals regional cellular junction nanoarchitecture previously uncharacterized, providing new insight into potential trans‐compartmental modulation of protein functions.
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影响因子：
7.8
作者：
Furuse, Mikio;Hata, Masaki;Furuse, Kyoko;Yoshida, Yoko;Haratake, Akinori;Sugitani, Yoshinobu;Noda, Tetsuo;Kubo, Akiharu;Tsukita, Shoichiro
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影响因子：
37.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.1
作者：
Lu Z;Ding L;Lu Q;Chen YH
通讯作者：
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可控删除 Claudin-7 诱导小鼠小肠严重炎症。
影响因子：
3.1
作者：
Li WJ;Xu C;Wang K;Li TY;Wang XN;Yang H;Xing T;Li WX;Chen YH;Gao H;Ding L
通讯作者：
Ding L