Duguay Duke, Foty Ramsey A, Steinberg Malcolm S
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Dev Biol. 2003 Jan 15;253(2):309-23. doi: 10.1016/s0012-1606(02)00016-7.
It is widely held that segregation of tissues expressing different cadherins results from cadherin-subtype-specific binding specificities. This belief is based largely upon assays in which cells expressing different cadherin subtypes aggregate separately when shaken in suspension. In various combinations of L cells expressing NCAM, E-, P-, N-, R-, or B-cadherin, coaggregation occurred when shear forces were low or absent but could be selectively inhibited by high shear forces. Cells expressing P- vs E-cadherin coaggregated and then demixed, one population enveloping the other completely. To distinguish whether this demixing was due to differences in cadherin affinities or expression levels, the latter were varied systematically. Cells expressing either cadherin at a lower level became the enveloping layer, as predicted by the Differential Adhesion Hypothesis. However, when cadherin expression levels were equalized, cells expressing P- vs E-cadherin remained intermixed. In this combination, "homocadherin" (E-E; P-P) and "heterocadherin" (E-P) adhesions must therefore be of similar strength. Cells expressing R- vs B-cadherin coaggregated but demixed to produce configurations of incomplete envelopment. This signifies that R- to B-cadherin adhesions must be weaker than either "homocadherin" adhesion. Together, cadherin quantity and affinity control tissue segregation and assembly through specification of the relative intensities of mature cell-cell adhesions.
人们普遍认为，表达不同钙黏蛋白的组织分离是由钙黏蛋白亚型特异性结合特异性导致的。这一观点主要基于以下实验：将表达不同钙黏蛋白亚型的细胞在悬浮液中振荡时，它们会分别聚集。在表达神经细胞黏附分子（NCAM）、E - 钙黏蛋白、P - 钙黏蛋白、N - 钙黏蛋白、R - 钙黏蛋白或B - 钙黏蛋白的L细胞的各种组合中，当剪切力较低或不存在时会发生共聚集，但高剪切力可选择性地抑制共聚集。表达P - 钙黏蛋白与E - 钙黏蛋白的细胞先共聚集然后分开，其中一群细胞会完全包裹另一群细胞。为了区分这种分开是由于钙黏蛋白亲和力的差异还是表达水平的差异，系统地改变了后者。如差异黏附假说所预测的那样，表达水平较低的任何一种钙黏蛋白的细胞会成为包裹层。然而，当钙黏蛋白表达水平相等时，表达P - 钙黏蛋白与E - 钙黏蛋白的细胞仍会混合在一起。因此，在这种组合中，“同型钙黏蛋白”（E - E；P - P）和“异型钙黏蛋白”（E - P）的黏附力必定相似。表达R - 钙黏蛋白与B - 钙黏蛋白的细胞共聚集但分开，形成不完全包裹的结构。这表明R - 钙黏蛋白与B - 钙黏蛋白的黏附力必定比任何一种“同型钙黏蛋白”黏附力都弱。总之，钙黏蛋白的数量和亲和力通过确定成熟细胞间黏附的相对强度来控制组织的分离和组装。
