Lewis J E, Wahl J K, Sass K M, Jensen P J, Johnson K R, Wheelock M J
Department of Biology, University of Toledo, Ohio 43606, USA.
J Cell Biol. 1997 Feb 24;136(4):919-34. doi: 10.1083/jcb.136.4.919.
Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either beta-catenin or plakoglobin, which is linked to alpha-catenin, which is linked to the actin cytoskeleton. The desmosome is composed of transmembrane proteins of the broad cadherin family (desmogleins and desmocollins) that are linked to the intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in the assembly of desmosomes, we produced an epithelial cell line that does not express classical cadherins and hence is unable to organize desmosomes, even though it retains the requisite desmosomal components. Transfection of E-cadherin and/or P-cadherin into this cell line did not restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organization. These data suggest that plakoglobin, which is the only known common component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to assemble desmosomal components at regions of cell-cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of beta-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.
鳞状上皮细胞同时具有黏着连接和桥粒。这些细胞将桥粒蛋白组织成功能结构的能力取决于它们首先组织黏着连接的能力。由于黏着连接和桥粒是具有不同分子组成的独立结构，所以黏着连接的形成是桥粒形成的先决条件这一点并非显而易见。黏着连接由跨膜经典钙黏蛋白（鳞状上皮细胞中的E-钙黏蛋白和/或P-钙黏蛋白）组成，其与β-连环蛋白或桥粒斑珠蛋白相连，β-连环蛋白或桥粒斑珠蛋白又与α-连环蛋白相连，α-连环蛋白再与肌动蛋白细胞骨架相连。桥粒由广泛的钙黏蛋白家族的跨膜蛋白（桥粒芯糖蛋白和桥粒胶蛋白）组成，这些蛋白大概通过桥粒斑珠蛋白和桥粒斑蛋白与中间丝细胞骨架相连。为了开始研究黏着连接在桥粒组装中的作用，我们构建了一种上皮细胞系，该细胞系不表达经典钙黏蛋白，因此即使保留了必需的桥粒成分也无法组织形成桥粒。将E-钙黏蛋白和/或P-钙黏蛋白转染到该细胞系中并不能恢复其组织形成桥粒的能力；然而，桥粒斑珠蛋白与E-钙黏蛋白的过表达确实使得桥粒得以组织形成。这些数据表明，桥粒斑珠蛋白是黏着连接和桥粒唯一已知的共同成分，在细胞能够开始在细胞间接触区域组装桥粒成分之前，它必须在黏着连接中与E-钙黏蛋白相连。尽管在没有桥粒斑珠蛋白的情况下仅利用β-连环蛋白也能形成黏着连接，但这种连接无法支持桥粒的形成。因此，我们推测桥粒斑珠蛋白在桥粒组织形成中发挥信号作用。
