The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes.
The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes.
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DOI：
10.1083/jcb.139.3.773
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发表时间：
1997-11-03
影响因子：
7.8
通讯作者：
Green, KJ
中科院分区：
文献类型：
--
作者：
Kowalczyk, AP;Bornslaeger, EA;Borgwardt, JE;Palka, HL;Dhaliwal, AS;Corcoran, CM;Denning, MF;Green, KJ
桥粒是一个高度组织的质膜结构域，它将中间丝耦合到细胞间粘附区域的质膜上。桥粒含有两类钙粘蛋白、桥粒芯糖蛋白和桥粒胶蛋白，它们与细胞质蛋白斑珠蛋白结合。桥粒斑蛋白是一种桥粒成分，在连接中间丝网络与桥粒斑块方面发挥着关键作用，桥粒斑蛋白的氨基末端结构域将桥粒斑蛋白靶向桥粒。然而，尚未鉴定出与桥粒斑蛋白氨基末端结构域结合的桥粒蛋白。为了确定桥粒钙粘蛋白和斑球蛋白是否与桥斑蛋白的氨基末端结构域相互作用，这些蛋白质在 L 细胞成纤维细胞（通常不表达桥粒成分的细胞）中共表达。当在 L 细胞中表达时，桥粒钙粘蛋白和斑珠蛋白表现出弥散分布。然而，在存在氨基末端桥粒斑蛋白多肽（DP-NTP）的情况下，在也含有DP-NTP的点状簇中观察到桥粒钙粘蛋白和斑珠蛋白。此外，斑珠蛋白和 DP-NTP 被募集到 L 细胞中的细胞-细胞界面，该细胞共表达嵌合钙粘蛋白、E-钙粘蛋白胞外结构域和桥粒芯糖蛋白-1 胞质结构域，这些细胞形成了超微结构与桥粒外斑相似的结构。在 COS 细胞瞬时表达实验中，嵌合体将 DP-NTP 募集到细胞边界需要斑球蛋白的共表达。从 L 细胞中提取时，斑球蛋白和 DP-NTP 共免疫沉淀，酵母两种杂交分析表明 DP-NTP 直接与斑球蛋白结合，但不与 Dsg1 结合。这些结果确定了桥粒斑蛋白在组织桥粒钙粘蛋白-斑球蛋白复合物中的作用，并为桥粒斑块中发生的蛋白质相互作用的层次结构提供了新的见解。
The desmosome is a highly organized plasma membrane domain that couples intermediate filaments to the plasma membrane at regions of cell–cell adhesion. Desmosomes contain two classes of cadherins, desmogleins, and desmocollins, that bind to the cytoplasmic protein plakoglobin. Desmoplakin is a desmosomal component that plays a critical role in linking intermediate filament networks to the desmosomal plaque, and the amino-terminal domain of desmoplakin targets desmoplakin to the desmosome. However, the desmosomal protein(s) that bind the amino-terminal domain of desmoplakin have not been identified. To determine if the desmosomal cadherins and plakoglobin interact with the amino-terminal domain of desmoplakin, these proteins were co-expressed in L-cell fibroblasts, cells that do not normally express desmosomal components. When expressed in L-cells, the desmosomal cadherins and plakoglobin exhibited a diffuse distribution. However, in the presence of an amino-terminal desmoplakin polypeptide (DP-NTP), the desmosomal cadherins and plakoglobin were observed in punctate clusters that also contained DP-NTP. In addition, plakoglobin and DP-NTP were recruited to cell–cell interfaces in L-cells co-expressing a chimeric cadherin with the E-cadherin extracellular domain and the desmoglein-1 cytoplasmic domain, and these cells formed structures that were ultrastructurally similar to the outer plaque of the desmosome. In transient expression experiments in COS cells, the recruitment of DP-NTP to cell borders by the chimera required co-expression of plakoglobin. Plakoglobin and DP-NTP co-immunoprecipitated when extracted from L-cells, and yeast two hybrid analysis indicated that DP-NTP binds directly to plakoglobin but not Dsg1. These results identify a role for desmoplakin in organizing the desmosomal cadherin–plakoglobin complex and provide new insights into the hierarchy of protein interactions that occur in the desmosomal plaque.
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影响因子：
7.8
作者：
Hinck, L;Nelson, W J;Papkoff, J
通讯作者：
Papkoff, J
影响因子：
2.7
作者：
Bierkamp, C;McLaughlin, KJ;Kemler, R
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影响因子：
7.5
作者：
Cowin, P;Burke, B
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Burke, B
影响因子：
4.8
作者：
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Kemler, R
影响因子：
7.8
作者：
Chitaev, NA;Leube, RE;Troyanovsky, RB;Eshkind, LG;Franke, WW;Troyanovsky, SM
通讯作者：
Troyanovsky, SM