Abstract
We have found that epithelial cells engage in a process of cadherin-mediated intercellular adhesion that utilizes calcium and actin polymerization in unexpected ways. Calcium stimulates filopodia, which penetrate and embed into neighboring cells. E-cadherin complexes cluster at filopodia tips, generating a two-rowed zipper of embedded puncta. Opposing cell surfaces are clamped by desmosomes, while vinculin, zyxin, VASP, and Mena are recruited to adhesion zippers by a mechanism that requires alpha-catenin. Actin reorganizes 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 function, filopodia embed, but actin reorganization/polymerization is prevented, and membranes cannot seal. Taken together, a dynamic mechanism for intercellular adhesion is unveiled involving calcium-activated filopodia penetration and VASP/Mena-dependent actin reorganization/polymerization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / analysis
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Actins / metabolism*
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Animals
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Animals, Newborn
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Cadherins / physiology
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Calcium / metabolism
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Carrier Proteins / analysis
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Carrier Proteins / metabolism
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Cell Adhesion / physiology
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Cell Adhesion Molecules / analysis
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Cell Adhesion Molecules / metabolism
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Fluorescent Antibody Technique
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In Vitro Techniques
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Intercellular Junctions / physiology
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Intercellular Junctions / ultrastructure
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Keratinocytes / chemistry
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Keratinocytes / cytology*
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Keratinocytes / metabolism*
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Metalloproteins / analysis
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Metalloproteins / metabolism
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Mice
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Mice, Knockout
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Microfilament Proteins
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Microscopy, Immunoelectron
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Phosphoproteins / analysis
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Phosphoproteins / metabolism
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Polymers / metabolism
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Pseudopodia / physiology
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Pseudopodia / ultrastructure
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Stress, Mechanical
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Vinculin / analysis
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Vinculin / metabolism
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Zyxin
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alpha Catenin
Substances
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Actins
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Cadherins
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Carrier Proteins
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Cell Adhesion Molecules
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Ctnna1 protein, mouse
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Cytoskeletal Proteins
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Enah protein, mouse
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Metalloproteins
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Microfilament Proteins
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Phosphoproteins
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Polymers
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Zyx protein, mouse
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Zyxin
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alpha Catenin
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vasodilator-stimulated phosphoprotein
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Vinculin
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Calcium