Abe Kentaro, Takeichi Masatoshi
RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):13-9. doi: 10.1073/pnas.0710504105. Epub 2007 Dec 18.
The cadherin-catenin complex is the major machinery for cell-cell adhesion in many animal species. This complex in general associates with actin fibers at its cytoplasmic side, organizing the adherens junction (AJ). In epithelial cells, the AJ encircles the cells near their apical surface and forms the "zonula adherens" or "adhesion belt." The mechanism as to how the cadherin-catenin complex and F-actin cooperate to generate these junctional structures, however, remains unknown. Here, we show that EPLIN (epithelial protein lost in neoplasm; also known as Lima-1), an actin-binding protein, couples with alpha-catenin and, in turn, links the cadherin-catenin complex to F-actin. Without EPLIN, this linkage was unable to form. When EPLIN had been depleted in epithelial cells, the adhesion belt was disorganized and converted into zipper-like junctions in which actin fibers were radially arranged. However, nonjunctional actin fibers were not particularly affected by EPLIN depletion. As EPLIN is known to have the ability to suppress actin depolymerization, our results suggest that EPLIN functions to link the cadherin-catenin complex to F-actin and simultaneously stabilizes this population of actin fibers, resulting in the establishment of the adhesion belt.
钙黏蛋白 - 连环蛋白复合体是许多动物物种中细胞间黏附的主要机制。该复合体通常在其细胞质一侧与肌动蛋白纤维结合，从而构建黏着连接（AJ）。在上皮细胞中，AJ环绕细胞靠近其顶端表面的部位，形成“黏着小带”或“黏附带”。然而，钙黏蛋白 - 连环蛋白复合体与F - 肌动蛋白如何协同作用以产生这些连接结构的机制仍不清楚。在此，我们表明EPLIN（肿瘤中缺失的上皮蛋白；也称为Lima - 1），一种肌动蛋白结合蛋白，与α - 连环蛋白结合，进而将钙黏蛋白 - 连环蛋白复合体与F - 肌动蛋白连接起来。没有EPLIN，这种连接就无法形成。当EPLIN在上皮细胞中被耗尽时，黏附带会紊乱并转变为拉链样连接，其中肌动蛋白纤维呈放射状排列。然而，非连接性肌动蛋白纤维并未受到EPLIN耗尽的特别影响。由于已知EPLIN具有抑制肌动蛋白解聚的能力，我们的结果表明EPLIN的功能是将钙黏蛋白 - 连环蛋白复合体与F - 肌动蛋白连接起来，并同时稳定这部分肌动蛋白纤维，从而形成黏附带。
