Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.
Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.
复制标题
DOI：
10.1091/mbc.e13-07-0357
复制
发表时间：
2013-12
影响因子：
3.3
通讯作者：
Kikuchi A
中科院分区：
文献类型：
--
作者：
Gon H;Fumoto K;Ku Y;Matsumoto S;Kikuchi A
Wnt信号在极化中起重要作用。在这里，肠上皮细胞显示，形成apicobasal极化在单细胞水平的细胞外基质粘附依赖的方式。Wnt 5a信号通过空间上Rac 1和RhoA活性之间的平衡控制促进单细胞极化。单个上皮来源的肿瘤细胞已被证明通过表达极化相关蛋白来诱导顶端和基底侧（AB）极性。然而，单个正常上皮细胞AB极化的生理线索和分子机制尚不清楚。当肠上皮细胞6（IEC 6细胞）接种在基底膜蛋白（基质胶），单细胞形成的F-肌动蛋白帽上的细胞表面上，其中顶端的标志物积累，和基底外侧的标志物被定位到其余的细胞表面区域，在Wnt 5a信号依赖的方式。然而，这些表型不诱导I型胶原。Rac 1活性在noncap区高于帽区，而Rho活性增加向帽区。Wnt 5a信号分别通过Tiam 1和p190 RhoGAP-A独立激活和抑制Rac 1和RhoA，后者与Dishevelled形成三级复合物。此外，通过Rac 1和RhoA的Wnt 5a信号传导是IEC 6细胞的囊形成所必需的。这些结果表明，Wnt 5a通过调节Rac和Rho活性以依赖于与特定细胞外基质蛋白的粘附的方式促进IEC 6细胞的AB极化。
Wnt signal plays important roles in polarization. Here intestinal epithelial cells are shown to form apicobasal polarization at a single-cell level in an extracellular matrix adhesion–dependent manner. Wnt5a signaling promotes single-cell polarization through balanced control between Rac1 and RhoA activities spatially. Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling–dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.