Sorting of cadherin–catenin-associated proteins into individual clusters
Sorting of cadherin–catenin-associated proteins into individual clusters
复制标题
将钙粘蛋白-连环蛋白相关蛋白分类到各个簇中
DOI：
10.1073/pnas.2105550118
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Troyanovsky, Sergey M.
中科院分区：
文献类型：
--
作者：
Troyanovsky, Regina B.;Sergeeva, Alina P.;Indra, Indrajyoti;Chen, Chi-Shuo;Kato, Rei;Shapiro, Lawrence;Honig, Barry;Troyanovsky, Sergey M.
经典钙粘附素的胞质尾巴形成多蛋白钙粘附素-连环蛋白复合体(CCC)，构成黏附连接(AJs)的主要结构单位。AJS中的Ccc形成连接簇，即“E簇”，由钙粘蛋白胞外结构域中的顺式和反式相互作用驱动，并由α-连环蛋白-肌动蛋白相互作用稳定。已知有更多的蛋白质与CCC的细胞质区域结合。在这里，我们分析这些CCC相关蛋白(CAP)如何整合到钙粘素簇中，以及它们如何影响簇过程。利用交联质谱联用的方法，我们发现大多数CAPS，包括力敏感蛋白vinculin，都与AJs外的CCCS相互作用。因此，结构建模表明，没有足够的空间让纽蛋白大小的帽整合到E簇中。以Scribble和Erbin两个大写字母为例，我们提供了这些蛋白质形成独立簇的证据，我们称之为“C簇”。作为原理的证明，我们通过使用钙粘素胞外区单抗(MAbs)证明，mAb结合的E-cadherin形成了经历交叉作用的单独的簇。综上所述，我们的数据表明，除了在细胞间黏附中发挥作用外，CAP驱动的CCC聚簇还用于将细胞质蛋白质组织到不同的结构域中，这些结构域可能同步组织内相邻细胞的信号网络。
The cytoplasmic tails of classical cadherins form a multiprotein cadherin–catenin complex (CCC) that constitutes the major structural unit of adherens junctions (AJs). The CCC in AJs forms junctional clusters, “E clusters,” driven bycisandtransinteractions in the cadherin ectodomain and stabilized by α-catenin–actin interactions. Additional proteins are known to bind to the cytoplasmic region of the CCC. Here, we analyze how these CCC-associated proteins (CAPs) integrate into cadherin clusters and how they affect the clustering process. Using a cross-linking approach coupled with mass spectrometry, we found that the majority of CAPs, including the force-sensing protein vinculin, interact with CCCs outside of AJs. Accordingly, structural modeling shows that there is not enough space for CAPs the size of vinculin to integrate into E clusters. Using two CAPs, scribble and erbin, as examples, we provide evidence that these proteins form separate clusters, which we term “C clusters.” As proof of principle, we show, by using cadherin ectodomain monoclonal antibodies (mAbs), that mAb-bound E-cadherin forms separate clusters that undergotransinteractions. Taken together, our data suggest that, in addition to its role in cell–cell adhesion, CAP-driven CCC clustering serves to organize cytoplasmic proteins into distinct domains that may synchronize signaling networks of neighboring cells within tissues.
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影响因子：
5.7
作者：
Borgon, RA;Vonrhein, C;Izard, T
通讯作者：
Izard, T
影响因子：
5.7
作者：
Harrison, Oliver J.;Jin, Xiangshu;Hong, Soonjin;Bahna, Fabiana;Ahlsen, Goran;Brasch, Julia;Wu, Yinghao;Vendome, Jeremie;Felsovalyi, Klara;Hampton, Cheri M.;Troyanovsky, Regina B.;Ben-Shau, Avinoam;Frank, Joachim;Troyanovsky, Sergey M.;Shapiro, Lawrence;Honig, Barry
通讯作者：
Honig, Barry
影响因子：
7.7
作者：
Mei L;Espinosa de Los Reyes S;Reynolds MJ;Leicher R;Liu S;Alushin GM
通讯作者：
Alushin GM
DOI：
10.1073/pnas.1911489116
发表时间：
2019-10-22
影响因子：
11.1
作者：
Bush, Martin;Alhanshali, Bashir M.;Bu, Zimei
通讯作者：
Bu, Zimei
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影响因子：
3.8
作者：
N. McNutt;Ronald S. Weinstein
通讯作者：
Ronald S. Weinstein