Tight junctions are specialized apical junctional complexes that help to maintain epithelial cell polarity. Two polarity-regulating protein complexes – Crumbs and Par6 – localize to the tight junctions of mammalian epithelial cells. Now, Ben Margolis and co-workers report that multiple regions of the transmembrane protein Crumbs3, which together with PALS1 and PATJ forms the Crumbs complex, are required for tight junction formation in the human mammary epithelial cell line MCF10A (see ). MCF10A cells normally express very little Crumbs3 and do not form functional tight junctions in vitro. The authors show that expression of exogenous Crumbs3 in MCF10A induces the formation of functional tight junctions. Mutations in the domains in Crumbs3 that interact with PDZ and FERM domains of other proteins disrupt the ability of Crumbs3 to promote tight junction formation. The authors therefore suggest that Crumbs3 promotes tight junction formation by recruiting and stabilizing PALS1 and proteins in the Par6 complex through their PDZ domains and unknown proteins through their FERM domains.
