Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants
Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants
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DOI：
10.1016/s0012-1606(02)00016-7
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发表时间：
2003-01-15
影响因子：
2.7
通讯作者：
Steinberg, MS
中科院分区：
文献类型：
--
作者：
Duguay, D;Foty, RA;Steinberg, MS
人们普遍认为，分离组织表达不同的钙粘蛋白的结果从钙粘蛋白亚型特异性结合特异性。这一观点主要基于表达不同钙粘蛋白亚型的细胞在悬浮液中摇动时分别聚集的测定。在表达NCAM、E-、P-、N、R-或B-钙粘蛋白的L细胞的各种组合中，当剪切力低或不存在时发生共聚集，但可被高剪切力选择性抑制。表达P-与E-钙粘蛋白的细胞共聚集，然后分层，一个群体完全包围另一个。为了区分这种分层是否是由于钙粘蛋白亲和力或表达水平的差异，后者是系统变化的。细胞表达钙粘蛋白在较低的水平成为包膜层，预测的差异粘附假说。然而，当钙粘蛋白表达水平相等时，表达P-与E-钙粘蛋白的细胞保持混合。在这种组合中，“同钙粘蛋白”（E-E; P-P）和“异钙粘蛋白”（E-P）粘附因此必须具有相似的强度。表达R-与B-钙粘蛋白的细胞共聚集但分层，产生不完全的聚集构型。这意味着R-至B-钙粘蛋白的粘附必须弱于“同型钙粘蛋白”的粘附。总之，钙粘蛋白的数量和亲和力通过成熟细胞-细胞粘附的相对强度的规格来控制组织分离和组装。(C)2003 Elsevier Science（美国）。All rights reserved.
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. (C) 2003 Elsevier Science (USA). All rights reserved.