Inhibiting cadherin function by dominant mutant E-cadherin expression increases the extent of tight junction assembly

Previous studies have shown that induction of cadherin-mediated cell-cell a dhesion leads to tight junction formation, and that blocking cadherin-media ted cell-cell adhesion inhibits tight junction assembly. Here we report ana lysis of tight junction assembly in MDCK cells overexpressing a mutant E-ca dherin protein that lacks an adhesive extracellular domain (T151 cells). Mu tant E-cadherin overexpression caused a dramatic reduction in endogenous ca dherin levels. Despite this, tight junction assembly was extensive. The num ber of tight junction strands observed by freeze-fracture electron microsco py significantly increased in T151 cells compared to that in control cells, Our data indicate that the hierarchical regulation of junctional complex a ssembly is not absolute, and that inhibition of cadherin function has both positive and negative effects on tight junction assembly.