Tight junctions (TJs) are formed at the apical side of adherens junctions (AJs) in epithelial cells. Major cell adhesion molecules (CAMs) at TJs are JAM and claudin, whereas major CAMs at AJs are nectin and cadherin. We previously showed that nectin initially forms cell–cell adhesion and then recruits cadherin to the nectin‐based cell–cell adhesion sites to form AJs, followed by the recruitment of JAM and claudin to the apical side of AJs to form TJs. We investigated the roles of nectin in the formation of TJs by expressing various combinations of CAMs in L fibroblasts with no TJs or AJs. Co‐expression of one of the AJ CAMs and one of the TJ CAMs formed two separate cell–cell adhesion membrane domains (CAMDs). Co‐expression of nectin‐3 and E‐cadherin formed the same CAMD, but co‐expression of JAM‐A and claudin‐1 did not form the same CAMD. Co‐expression of JAM‐A and claudin‐1 with nectin‐3, but not E‐cadherin, made them form the same CAMD, which was separated from the nectin‐based CAMD. Nectin‐3 required afadin, a nectin‐ and F‐actin‐binding protein, for this ability. In conclusion, nectin plays a novel role in the co‐localization of JAM and claudin at the same CAMD.
5CREST, JST, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanTight junctions (TJs) and adherens junctions (AJs) form an apical junctional complex at the apical side of the lateral membranes of epithelial cells, in which TJs are aligned at the apical side of AJs. Many cell adhesion molecules (CAMs) and cell polarity molecules (CPMs) cooperatively regulate the formation of the apical junctional complex, but the mechanism for the alignment of TJs at the apical side of AJs is not fully understood. We developed a cellular system with which epithelial-like TJs and AJs were reconstituted in fibroblasts and analyzed the cooperative roles of CAMs and CPMs. We exogenously expressed various combinations of CAMs and CPMs in fibroblasts that express negligible amounts of these molecules endogenously. In these cells, the nectin-based cell-cell adhesion was formed at the apical side of the junctional adhesion molecule (JAM)-based cell-cell adhesion, and cadherin and claudin were recruited to the nectin-3-and JAM-based cell-cell adhesion sites to form AJ-like and TJ-like domains, respectively. This inversed alignment of the AJ-like and TJ-like domains was reversed by complementary expression of CPMs Par-3, atypical protein kinase C, Par-6, Crb3, Pals1 and Patj. We describe the cooperative roles of these CAMs and CPMs in the apico-basal alignment of TJs and AJs in epithelial cells.
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