The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)

The establishment and maintenance of cellular polarity are critical for the development of multicellular organisms. PAR (partitioning-defective) prote ins were identified in Caenorhabditis elegans as determinants of asymmetric cell division and polarized cell growth. Recently, vertebrate orthologues of two of these proteins, ASIP/PAR-3 and PAR-6, were found to form a signal ling complex with the small GTPases Cdc42/Rac1 and with atypical protein ki nase C (PKC). Here we show that ASIP/PAR-3 associates with the tight-juncti on-associated protein junctional adhesion molecule (JAM) in vitro and in vi vo. No binding was observed with claudin-1, -4 or -5. In fibroblasts and CH O cells overexpressing JAM, endogenous ASIP is recruited to JAM at sites of cell-cell contact. Overexpression of truncated JAM lacking the extracellul ar part disrupts ASIP/PAR-3 localization at intercellular junctions and del ays ASIP/PAR-3 recruitment to newly formed cell junctions. During junction formation, JAM appears early in primordial forms of junctions. Our data sug gest that the ASIP/PAR-3-aPKC complex is tethered to tight junctions via it s association with JAM, indicating a potential role for JAM in the generati on of cell polarity in epithelial cells.