The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity
The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity
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DOI：
10.1242/jcs.00704
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发表时间：
2003-10-01
影响因子：
4
通讯作者：
Vestweber, D
中科院分区：
文献类型：
--
作者：
Ebnet, K;Aurrand-Lions, M;Vestweber, D
紧密连接在脊椎动物内皮细胞和上皮细胞的细胞极性建立中起着重要作用。由细胞极性蛋白PAR-3和PAR-6以及非典型蛋白激酶C组成的三元蛋白复合物定位于紧密连接处，并且对于紧密连接的形成至关重要。我们最近发现，PAR-3直接与连接粘附分子（JAM），这表明三元复合物是针对上皮细胞的紧密连接，通过PAR-3结合到JAM。由内皮细胞表达的JAM相关蛋白促使我们测试是否可以通过结合JAM-2、JAM-3、内皮细胞选择性粘附分子（ESAM）或科萨基和腺病毒受体（CAR）来在内皮细胞中发生三元复合物的募集。在这里，我们表明，两个JAM相关的蛋白质JAM-2和JAM-3直接与PAR-3。PAR-3和JAM-2/-3之间的关联通过PAR-3的第一个PDZ结构域介导。与JAM-2和JAM-3在内皮细胞中的主要表达一致，我们发现PAR-3在体内由内皮细胞表达，并且定位于培养的内皮细胞的细胞接触处。PAR-3与JAM-2/-3相关，但不与JAM相关的Ig超家族成员ESAM或CAR相关。此外，我们发现紧密连接相关蛋白ZO-1与JAM-2/-3以PDZ结构域依赖的方式相关联。使用异位表达的JAM-2在CHO细胞中，我们表明，连接定位的JAM-2调节丝氨酸磷酸化和聚集在细胞-细胞接触招募内源性PAR-3和ZO-1。我们的研究结果表明，JAM-2通过其在细胞间接触的调节聚集来影响内皮细胞连接，并且他们支持JAM-2和可能的JAM-3在内皮细胞紧密连接形成中的作用。
Tight junctions play a central role in the establishment of cell polarity in vertebrate endothelial and epithelial cells. A ternary protein complex consisting of the cell polarity proteins PAR-3 and PAR-6 and the atypical protein kinase C localizes at tight junctions and is crucial for tight junction formation. We have recently shown that PAR-3 directly associates with the junctional adhesion molecule (JAM), which suggests that the ternary complex is targeted to tight junctions of epithelial cells through PAR-3 binding to JAM. The expression of JAM-related proteins by endothelial cells prompted us to test whether recruitment of the ternary complex in endothelial cells can occur through binding to JAM-2, JAM-3, endothelial cell-selective adhesion molecule (ESAM) or coxsackie- and adenovirus receptor (CAR). Here we show that the two JAM-related proteins JAM-2 and JAM-3 directly associate with PAR-3. The association between PAR-3 and JAM-2/-3 is mediated through the first PDZ domain of PAR-3. In agreement with the predominant expression of JAM-2 and JAM-3 in endothelial cells, we found that PAR-3 is expressed by endothelial cells in vivo and is localized at cell contacts of cultured endothelial cells. PAR-3 associates with JAM-2/-3 but not with the JAM-related Ig-superfamily members ESAM or CAR. In addition, we show that the tight junction-associated protein ZO-1 associates with JAM-2/-3 in a PDZ domain-dependent manner. Using ectopic expression of JAM-2 in CHO cells, we show that the junctional localization of JAM-2 is regulated by serine phosphorylation and that its clustering at cell-cell contacts recruits endogenous PAR-3 and ZO-1. Our findings suggest that JAM-2 affects endothelial cell junctions by its regulated clustering at intercellular contacts, and they support a role for JAM-2, and possibly JAM-3, in tight junction formation of endothelial cells.