Ebnet Klaus
Institute-associated Research Group: Cell adhesion and cell polarity; Institute of Medical Biochemistry; Center of Molecular Biology of Inflammation; University Muenster; Muenster, Germany.
Tissue Barriers. 2013 Jan 1;1(1):e22993. doi: 10.4161/tisb.22993.
Cell-cell adhesion plays a critical role in the formation of barrier-forming epithelia. The molecules which mediate cell-cell adhesion frequently act as signaling molecules by recruiting and/or assembling cytoplasmic protein complexes. Junctional Adhesion Molecule (JAM)-A interacts with the cell polarity protein PAR-3, a member of the PAR-3-aPKC-PAR-6 complex, which regulates the formation of cell-cell contacts and the development of tight junctions (TJs). In our recent study we found that JAM-A is localized at primordial, spot-like cell-cell junctions (pAJs) in a non-phosphorylated form. After the recruitment of the PAR-aPKC complex and its activation at pAJs, aPKC phosphorylates JAM-A at Ser285 to promote the maturation of immature junctions. In polarized epithelial cells, aPKC phosphorylates JAM-A selectively at the TJs to maintain the barrier function of TJs. Thus, through mutual regulation, JAM-A and aPKC form a functional unit that regulates the establishment of barrier-forming junctions in vertebrate epithelial cells.
细胞间黏附在形成屏障的上皮细胞形成过程中起着关键作用。介导细胞间黏附的分子常常通过招募和/或组装细胞质蛋白复合物来充当信号分子。连接黏附分子（JAM）-A与细胞极性蛋白PAR-3相互作用，PAR-3是PAR-3-aPKC-PAR-6复合物的成员，该复合物调节细胞间接触的形成和紧密连接（TJ）的发育。在我们最近的研究中，我们发现JAM-A以非磷酸化形式定位于原始的、点状的细胞间连接（pAJ）处。在PAR-aPKC复合物在pAJ处募集并激活后，aPKC使JAM-A的Ser285位点磷酸化，以促进未成熟连接的成熟。在极化上皮细胞中，aPKC在TJ处选择性地使JAM-A磷酸化，以维持TJ的屏障功能。因此，通过相互调节，JAM-A和aPKC形成一个功能单元，调节脊椎动物上皮细胞中屏障形成连接的建立。
