RIKEN Center for Developmental Biology, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
J Cell Biol. 2011 Aug 22;194(4):643-56. doi: 10.1083/jcb.201104124. Epub 2011 Aug 15.
The zonula adherens (ZA), a type of adherens junction (AJ), plays a major role in epithelial cell-cell adhesions. It remains unknown how the ZA is remodeled during epithelial reorganization. Here we found that the ZA was converted to another type of AJ with punctate morphology (pAJ) at the margins of epithelial colonies. The F-actin-stabilizing protein EPLIN (epithelial protein lost in neoplasm), which functions to maintain the ZA via its association with αE-catenin, was lost in the pAJs. Consistently, a fusion of αE-catenin and EPLIN contributed to the formation of ZA but not pAJs. We show that junctional tension was important for retaining EPLIN at AJs, and another force derived from actin fibers laterally attached to the pAJs inhibited EPLIN-AJ association. Vinculin was required for general AJ formation, and it cooperated with EPLIN to maintain the ZA. These findings suggest that epithelial cells remodel their junctional architecture by responding to mechanical forces, and the αE-catenin-bound EPLIN acts as a mechanosensitive regulator for this process.
粘着连接(AJ)中的一种——粘着带(ZA),在维持上皮细胞间的黏附连接中发挥着重要作用。然而,上皮细胞在重排过程中如何重塑 ZA 尚不清楚。本研究发现,上皮细胞集落边缘的 ZA 转换为另一种具有点状形态的 AJ(pAJ)。EPLIN(肿瘤中丢失的上皮蛋白)是一种稳定 F-actin 的蛋白,通过与αE-连环蛋白的结合来维持 ZA,而在 pAJ 中却丢失了。同样,αE-连环蛋白和 EPLIN 的融合有助于 ZA 的形成,但不能形成 pAJ。我们发现,连接张力对于 EPLIN 在 AJ 中的保留很重要,而来自侧向附着在 pAJ 上的肌动蛋白纤维的另一种力抑制了 EPLIN-AJ 结合。桩蛋白对于一般 AJ 的形成是必需的,它与 EPLIN 合作来维持 ZA。这些发现表明,上皮细胞通过响应机械力重塑其连接结构,并且与αE-连环蛋白结合的 EPLIN 作为该过程的机械敏感调节剂。