Involvement of nectin in the localization of junctional adhesion molecule at tight junctions.

Junctional adhesion molecule (JAM) is a Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which localizes at tight junctions (TJs). Claudin is a key cell-cell adhesion molecule that forms TJ strands at TJs. JAM is associated with claudin through their cytoplasmic tail-binding protein, ZO-1. JAM is furthermore associated with Par-3, a cell polarity protein which forms a ternary complex with Par-6 and atypical protein kinase C. Nectin is another Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which localizes at adherens junctions (AJs). Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs cooperatively with E-cadherin. We show here that nectin is furthermore involved in the localization of JAM at TJs. During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, JAM was recruited to the nectin-based cell-cell adhesion sites. This recruitment of JAM was inhibited by nectin inhibitors, which inhibited the trans-interaction of nectin. Microbeads coated with the extracellular fragment of nectin, that interacted with cellular nectin, also recruited JAM to the bead-MDCK cell contact sites. Furthermore, when cadherin-deficient L fibroblasts stably expressing both exogenous JAM and nectin (nectin-JAM-L cells) were co-cultured with L fibroblasts expressing only nectin (nectin-L cells), JAM was concentrated at the cell-cell adhesion sites between nectin-JAM-L and nectin-L cells without the trans-interaction of JAM. Analyses of the localization and immunoprecipitation of JAM revealed that it was associated with nectin through afadin and ZO-1. These results suggest that nectin has a role in the localization of JAM at TJs in the process of the formation of the junctional complex in epithelial cells.

Fukuhara A ，Irie K ，Nakanishi H ，Takekuni K ，Kawakatsu T ，Ikeda W ，Yamada A ，Katata T ，Honda T ，Sato T ，Shimizu K ，Ozaki H ，Horiuchi H ，Kita T ，Takai Y ... -  《ONCOGENE》

Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions.

Ooshio T ，Fujita N ，Yamada A ，Sato T ，Kitagawa Y ，Okamoto R ，Nakata S ，Miki A ，Irie K ，Takai Y ... -  《JOURNAL OF CELL SCIENCE》

Novel role of nectin: implication in the co-localization of JAM-A and claudin-1 at the same cell-cell adhesion membrane domain.

Kuramitsu K ，Ikeda W ，Inoue N ，Tamaru Y ，Takai Y ... -  《-》

Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions.

Itoh M ，Sasaki H ，Furuse M ，Ozaki H ，Kita T ，Tsukita S ... -  《-》

Involvement of heterophilic trans-interaction of Necl-5/Tage4/PVR/CD155 with nectin-3 in formation of nectin- and cadherin-based adherens junctions.

Sato T ，Irie K ，Ooshio T ，Ikeda W ，Takai Y ... -  《GENES TO CELLS》