Gkretsi Vasiliki, Zhang Yongjun, Tu Yizeng, Chen Ka, Stolz Donna B, Yang Yanqiang, Watkins Simon C, Wu Chuanyue
Department of Pathology, Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Cell Sci. 2005 Feb 15;118(Pt 4):697-710. doi: 10.1242/jcs.01638. Epub 2005 Jan 25.
Cell-cell junctions are essential for epithelial and endothelial tissue formation and communication between neighboring cells. We report here that migfilin, a recently identified component of cell-extracellular matrix adhesions, is recruited to cell-cell junctions in response to cadherin-mediated cell-cell adhesions. Migfilin is detected at cell-cell junctions in both epithelial and endothelial cells. It forms detergent-resistant, discrete clusters that associate with actin bundles bridging neighboring cells. Immunoelectron microscopic analyses reveal that migfilin is closely associated with beta-catenin, but not desmosomes, at cell-cell junctions. Furthermore, we show that the C-terminal LIM domains, but not its N-terminal domain, mediates migfilin localization to cell-cell junctions. The site mediating the localization of migfilin to cell-cell junctions at least partially overlaps with that mediating the localization of migfilin to cell-ECM adhesions. Finally, siRNA-mediated depletion of migfilin compromised the organization of adherens junctions and weakened cell-cell association. These results identify migfilin as a component of adherens junctions and suggest an important role for migfilin in the organization of the cell-cell adhesion structure.
细胞间连接对于上皮组织和内皮组织的形成以及相邻细胞间的通讯至关重要。我们在此报告，migfilin是一种最近被鉴定出的细胞-细胞外基质黏附成分，它会响应钙黏蛋白介导的细胞间黏附而被招募到细胞间连接部位。在上皮细胞和内皮细胞的细胞间连接部位均能检测到migfilin。它形成耐去污剂的离散簇，与连接相邻细胞的肌动蛋白束相关联。免疫电子显微镜分析显示，在细胞间连接部位，migfilin与β-连环蛋白紧密相关，但与桥粒无关。此外，我们表明，migfilin的C端LIM结构域而非其N端结构域介导了migfilin定位于细胞间连接部位。介导migfilin定位于细胞间连接部位的位点至少部分与介导migfilin定位于细胞-细胞外基质黏附部位的位点重叠。最后，siRNA介导的migfilin缺失破坏了黏着连接的组织，并削弱了细胞间的联系。这些结果确定migfilin是黏着连接的一个组成部分，并表明migfilin在细胞间黏附结构的组织中起重要作用。
