Directed actin polymerization is the driving force for epithelial cell-cell adhesion

We have found that epithelial cells engage in a process of cadherin-mediate d intercellular adhesion that utilizes calcium and actin polymerization in unexpected ways. Calcium stimulates filopodia, which penetrate and embed in to neighboring cells. E-cadherin complexes cluster at filopodia tips, gener ating a two-rowed zipper of embedded puncta. Opposing cell surfaces are cla mped by desmosomes, while vinculin, zyxin, VASP, and Mena are recruited to adhesion zippers by a mechanism that requires alpha-catenin. Actin reorgani zes and polymerizes to merge puncta into a single row and seal cell borders . In keratinocytes either null for alpha-catenin or blocked in VASP/Mena fu nction, filopodia embed, but actin reorganization/polymerization is prevent ed, and membranes cannot seal. Taken together, a dynamic mechanism for inte rcellular adhesion is unveiled involving calcium-activated filopodia penetr ation and VASP/Mena-dependent actin reorganization/polymerization.