Kreft B, Berndorff D, Böttinger A, Finnemann S, Wedlich D, Hortsch M, Tauber R, Gessner R
Institute of Clinical Chemistry and Biochemistry, Humboldt-University Berlin, Germany.
J Cell Biol. 1997 Mar 10;136(5):1109-21. doi: 10.1083/jcb.136.5.1109.
The adhesive function of classical cadherins depends on the association with cytoplasmic proteins, termed catenins, which serve as a link between cadherins and the actin cytoskeleton. LI-cadherin, a structurally different member of the cadherin family, mediates Ca2+-dependent cell-cell adhesion, although its markedly short cytoplasmic domain exhibits no homology to this highly conserved region of classical cadherins. We now examined whether the adhesive function of LI-cadherin depends on the interaction with catenins, the actin cytoskeleton or other cytoplasmic components. In contrast to classical cadherins, LI-cadherin, when expressed in mouse L cells, was neither associated with catenins nor did it induce an upregulation of beta-catenin. Consistent with these findings, LI-cadherin was not resistant to detergent extraction and did not induce a reorganization of the actin cytoskeleton. However, LI-cadherin was still able to mediate Ca2+-dependent cell-cell adhesion. To analyze whether this function requires any interaction with proteins other than catenins, a glycosyl phosphatidylinositol-anchored form of LI-cadherin (LI-cadherin(GPI)) was constructed and expressed in Drosophila S2 cells. The mutant protein was able to induce Ca2+-dependent, homophilic cell-cell adhesion, and its adhesive properties were indistinguishable from those of wild type LI-cadherin. These findings indicate that the adhesive function of LI-cadherin is independent of any interaction with cytoplasmic components, and consequently should not be sensitive to regulatory mechanisms affecting the binding of classical cadherins to catenins and to the cytoskeleton. Thus, we postulate that the adhesive function of LI-cadherin is complementary to that of coexpressed classical cadherins ensuring cell-cell contacts even under conditions that downregulate the function of classical cadherins.
经典钙黏蛋白的黏附功能取决于与细胞质蛋白（称为连环蛋白）的结合，连环蛋白作为钙黏蛋白与肌动蛋白细胞骨架之间的连接。LI-钙黏蛋白是钙黏蛋白家族中结构不同的成员，介导钙离子依赖的细胞间黏附，尽管其明显较短的细胞质结构域与经典钙黏蛋白的这个高度保守区域没有同源性。我们现在研究了LI-钙黏蛋白的黏附功能是否依赖于与连环蛋白、肌动蛋白细胞骨架或其他细胞质成分的相互作用。与经典钙黏蛋白不同，LI-钙黏蛋白在小鼠L细胞中表达时，既不与连环蛋白结合，也不诱导β-连环蛋白的上调。与这些发现一致，LI-钙黏蛋白对去污剂提取不具有抗性，也不诱导肌动蛋白细胞骨架的重组。然而，LI-钙黏蛋白仍然能够介导钙离子依赖的细胞间黏附。为了分析这种功能是否需要与连环蛋白以外的蛋白质进行任何相互作用，构建了一种糖基磷脂酰肌醇锚定形式的LI-钙黏蛋白（LI-钙黏蛋白(GPI)）并在果蝇S2细胞中表达。突变蛋白能够诱导钙离子依赖的、同源性的细胞间黏附，其黏附特性与野生型LI-钙黏蛋白没有区别。这些发现表明，LI-钙黏蛋白的黏附功能独立于与细胞质成分的任何相互作用，因此不应受到影响经典钙黏蛋白与连环蛋白及细胞骨架结合的调节机制的影响。因此，我们推测LI-钙黏蛋白的黏附功能与共表达的经典钙黏蛋白的黏附功能互补，即使在下调经典钙黏蛋白功能的条件下也能确保细胞间接触。
