ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells
ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells
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DOI：
10.1046/j.1365-2443.2002.00533.x
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发表时间：
2002-05-01
期刊：
影响因子：
2.1
通讯作者：
Inagaki, M
中科院分区：
文献类型：
--
作者：
Izawa, I;Nishizawa, M;Inagaki, M
背景资料：ERBIN是一种ErbB 2受体相互作用蛋白，属于最近描述的一个蛋白家族，被命名为Leptin [leucine-rich repeats and PSD-95/dLg-A/ZO-1（PDZ）domains]家族，它在细胞极性的建立中具有重要作用。为了鉴定新的ERBIN结合蛋白，我们利用ERBIN羧基端含有PDZ结构域的片段作为诱饵，并且我们分离出p0071（也称为plakophilin-4）作为ERBIN相互作用蛋白。p0071是p120连环蛋白家族的成员，其被定义为具有10个Armadillo重复序列的蛋白质，并且定位于沿着细胞-细胞边界。ERBIN PDZ结构域结合含有PDZ结构域结合序列的p0071的COOH末端。内源性ER-BIN与p0071共免疫沉淀。在完全极化的Madin-Darby犬肾（MDCK）细胞中，ERBIN主要与β-连环蛋白共定位，部分与桥粒斑蛋白沿着侧质膜区域共定位。在这些细胞-细胞接触区域，ERBIN与p0071共定位。Cdc 42、Rac 1或RhoA、Rho家族小GTPases的主要活性形式的过表达导致ER-BIN在MDCK和HeLa细胞的细胞-细胞接触处显著积累。结论：ERBIN在体内与p0071相互作用，可能参与上皮细胞粘附连接和桥粒的组织化。此外，我们证明ER-BIN的亚细胞定位可能受到Rho家族小GTP酶的调节。
Background: ERBIN, an ErbB2 receptor-interacting protein, belongs to a recently described family of proteins termed the LAP [leucine-rich repeats and PSD-95/dLg-A/ZO-1 (PDZ) domains] family which has essential roles in establishment of cell polarity.Results: To identify new ERBIN-binding proteins, we screened a yeast two-hybrid library, using the carboxyl-terminal fragment of ER-BIN containing PDZ domain as the bait, and we isolated p0071 (also called plakophilin-4) as an ERBIN-interacting protein. p0071 is a member of the p120 catenin family, which are defined as proteins with 10 armadillo repeats, and localizes along the cell-cell border. The ERBIN PDZ domain binds the COOH-terminus of p0071 containing the PDZ domain-binding sequence. Endogenous ER-BIN was co-immunoprecipitated with p0071. In fully polarized Madin-Darby canine kidney (MDCK) cells, ERBIN co-localized largely with beta-catenin and partly with desmoplakin along the lateral plasma membrane domain. At these cell-cell contact regions, ERBIN co-localizes with p0071. Over-expression of the dominant active forms of Cdc42, Rac1 or RhoA, Rho family small GTPases, resulted in a marked accumulation of ER-BIN at the cell-cell contacts of MDCK and HeLa cells.Conclusion: These results show that ERBIN interacts in vivo with p0071 and that it may be involved in the organization of adherens junctions and the desmosomes of epithelia. In addition, we demonstrated that the subcellular localization of ER-BIN might be regulated by Rho family small GTPases.