Directed actin polymerization is the driving force for epithelial cell-cell adhesion.
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.
Vasioukhin
V
V
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA.
Bauer
C
C
Yin
M
M
Fuchs
E
E
D000199:Actins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000502:physiology / Q000648:ultrastructure; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D008667:Metalloproteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D016253:Microscopy, Immunoelectron; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology / Q000648:ultrastructure; D013314:Stress, Mechanical; D016596:Vinculin / Q000032:analysis / Q000378:metabolism; D060589:Zyxin; D051178:alpha Catenin; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D008667:Metalloproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011108:Polymers; C498285:Zyx protein, mouse; D060589:Zyxin; D051178:alpha Catenin; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin; D002118:Calcium