Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: Binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF
Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: Binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF
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DOI：
10.1091/mbc.e04-04-0350
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发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Hunziker, W
中科院分区：
文献类型：
--
作者：
Kausalya, PJ;Phua, DCY;Hunziker, W
ARVCF是p120(CTN)家族中的一种蝉重复蛋白，与经典钙粘附素结合，存在于黏附连接中，但其功能尚不清楚。在这里，我们证明了ARVCF通过C-末端PDZ结合基序与闭锁小带(ZO)-1和ZO-2相互作用。ARVCF和ZO-1部分共存于极化上皮Madin-Darby犬肾细胞的顶端黏附复合体附近。ARVCF、ZO-1和E-钙粘附素形成一个复合体，并在稀疏细胞培养中被招募到细胞与细胞的初始接触部位。ARVCF的E-钙粘附素结合和质膜定位需要PDZ结合基序。细胞间黏附的破坏会使ARVCF从质膜上释放出来，增加的蛋白质部分定位于细胞核。ARVCF的核定位也需要PDZ结合基序，并可由ZO-2的PDZ结构域介导。因此，ARVCF与不同的PDZ结构域蛋白的相互作用决定了它的亚细胞定位。特别是与ZO-1和ZO-2的相互作用，可能分别介导ARVCF募集到质膜和细胞核，可能是对细胞-细胞黏附信号的反应。
ARVCF, an armadillo-repeat protein of the p120(ctn) family, associates with classical cadherins and is present in adherens junctions, but its function is poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ-binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially colocalize in the vicinity of the apical adhesion complex in polarized epithelial Madin-Darby canine kidney cells. ARVCF, ZO-1, and E-cadherin form a complex and are recruited to sites of initial cell-cell contact in sparse cell cultures. E-cadherin binding and plasma membrane localization of ARVCF require the PDZ-binding motif. Disruption of cell-cell adhesion releases ARVCF from the plasma membrane and an increased fraction of the protein localizes to the nucleus. Nuclear localization of ARVCF also requires the PDZ-binding motif and can be mediated by the PDZ domains of ZO-2. Thus, the interaction of ARVCF with distinct PDZ-domain proteins determines its subcellular localization. Interactions with ZO-1 and ZO-2, in particular, may mediate recruitment of ARVCF to the plasma membrane and the nucleus, respectively, possibly in response to cell-cell adhesion cues.