Caveolin-1 expression inhibits Wnt/β-catenin/Lef-1 signaling by recruiting β-catenin to caveolae membrane domains
Caveolin-1 expression inhibits Wnt/β-catenin/Lef-1 signaling by recruiting β-catenin to caveolae membrane domains
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DOI：
10.1074/jbc.m002020200
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发表时间：
2000-07-28
影响因子：
4.8
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
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作者：
Galbiati, F;Volonte, D;Lisanti, MP
小窝蛋白-1是小窝膜的主要成分。在NIR 3 T3细胞中，小窝蛋白-1表达在融合细胞中显著上调，并定位于细胞-细胞接触区域。然而，目前尚不清楚小窝蛋白-1是否参与细胞间信号传导。在这里，我们研究了小窝蛋白-1在调节β-连环蛋白信号传导中的潜在作用。β-连环蛋白在细胞中起双重作用，将E-钙粘蛋白连接到肌动蛋白细胞骨架，并通过与淋巴增强因子（Lef-1）家族转录因子的成员形成复合物而在Wnt信号传导中起作用。我们发现，E钙粘蛋白，β-连环蛋白和γ-连环蛋白（斑珠蛋白）都集中在小窝膜。此外，我们证明，激活β-连环蛋白/Lef-1信号Wnt-1或过度表达β-连环蛋白本身被小窝蛋白-1的表达抑制。我们还表明，在小窝蛋白-1负细胞中重组表达小窝蛋白-1足以招募β-连环蛋白小窝膜，从而阻断β-连环蛋白介导的反式激活。这些结果表明，小窝蛋白-1的表达可以调节Wnt/β-catenin/Lef-1信号通过调节β-catenin的细胞内定位。
Caveolin-1 is a principal component of caveolae membranes. In NIR 3T3 cells, caveolin-1 expression is dramatically up-regulated in confluent cells and localizes at areas of cell-cell contact. However, it remains unknown whether caveolin-1 is involved in cell-cell signaling. Here, we examine the potential role of caveolin-1 in regulating beta-catenin signaling. beta-Catenin plays a dual role in the cell, Linking E-cadherin to the actin cytoskeleton and in Wnt signaling by forming a complex with members of the lymphoid enhancing factor (Lef-1) family of transcription factors. We show that E cadherin, beta-catenin, and gamma-catenin (plakoglobin) are all concentrated in caveolae membranes. Moreover, we demonstrate that activation of beta-catenin/Lef-1 signaling by Wnt-1 or by overexpression of beta-catenin itself is inhibited by caveolin-1 expression. We also show that recombinant expression of caveolin-1 in caveolin-1 negative cells is sufficient to recruit beta-catenin to caveolae membranes, thereby blocking beta-catenin-mediated transactivation. These results suggest that caveolin-1 expression can modulate Wnt/beta-catenin/Lef-1 signaling by regulating the intracellular localization of beta-catenin.