Flotillins directly interact with γ-catenin and regulate epithelial cell-cell adhesion.
Flotillins directly interact with γ-catenin and regulate epithelial cell-cell adhesion.
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DOI：
10.1371/journal.pone.0084393
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tikkanen R
中科院分区：
文献类型：
--
作者：
Kurrle N;Völlner F;Eming R;Hertl M;Banning A;Tikkanen R
Flotillin-1和flotillin-2是两个同源的膜筏相关蛋白。虽然有报道称flotillins参与细胞粘附过程并在乳腺癌进展中发挥作用，因此使其成为未来有趣的治疗靶点，但其确切功能尚未得到很好的阐明。本研究探讨了这些蛋白在非恶性细胞细胞间粘附中的作用。我们使用非恶性上皮细胞MCF10A来研究细胞-细胞粘附复合物中漂浮蛋白的相互作用网络。RNA干扰被用来检测flotillins对粘附连接结构的影响，以及对核心蛋白（如E-cadherin）与膜筏结合的影响。我们在这里表明，在MCF10A细胞和各种人类细胞系中，粘附连接的cadherin蛋白与flotilin -2结合。在体外，flotilin -1和flotilin -2直接与γ-catenin相互作用，γ-catenin是迄今为止已知的唯一一种既存在于粘附体连接又存在于桥粒的蛋白质。γ-catenin序列中相互作用域的定位确定了Armadillo结构域6-8，特别是ARM结构域7，与flotillins的关联是重要的。此外，flotillins的缺失显著影响了人上皮细胞MCF10A粘附连接的形态，并改变了E-cadherin和γ-catenin与膜筏的关联。综上所述，这些观察结果表明flotillins，特别是flotillin-2，在非恶性上皮细胞的细胞-细胞粘附中具有功能作用。
Flotillin-1 and flotillin-2 are two homologous, membrane raft associated proteins. Although it has been reported that flotillins are involved in cell adhesion processes and play a role during breast cancer progression, thus making them interesting future therapeutic targets, their precise function has not been well elucidated. The present study investigates the function of these proteins in cell-cell adhesion in non-malignant cells. We have used the non-malignant epithelial MCF10A cells to study the interaction network of flotillins within cell-cell adhesion complexes. RNA interference was used to examine the effect of flotillins on the structure of adherens junctions and on the association of core proteins, such as E-cadherin, with membrane rafts. We here show that the cadherin proteins of the adherens junction associate with flotillin-2 in MCF10A cells and in various human cell lines. In vitro, flotillin-1 and flotillin-2 directly interact with γ-catenin which is so far the only protein known to be present both in the adherens junction and the desmosome. Mapping of the interaction domain within the γ-catenin sequence identified the Armadillo domains 6–8, especially ARM domain 7, to be important for the association with flotillins. Furthermore, depletion of flotillins significantly influenced the morphology of the adherens junction in human epithelial MCF10A cells and altered the association of E-cadherin and γ-catenin with membrane rafts. Taken together, these observations suggest a functional role for flotillins, especially flotillin-2, in cell-cell adhesion in non-malignant epithelial cells.
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影响因子：
5.3
作者：
Bodrikov, Vsevolod;Solis, Gonzalo P.;Stuermer, Claudia A. O.
通讯作者：
Stuermer, Claudia A. O.
影响因子：
3.3
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Tikkanen, Ritva
影响因子：
21.3
作者：
Glebov, OO;Bright, NA;Nichols, BJ
通讯作者：
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影响因子：
4.8
作者：
Aberle, H;Schwartz, H;Kemler, R
通讯作者：
Kemler, R