Dynamic interplay between adhesive and lateral E-cadherin dimers.
E-cadherin, an adhesive transmembrane protein of epithelial adherens junctions, forms two types of detergent-resistant dimers: adhesive dimers consisting of cadherin molecules derived from two neighboring cells and lateral dimers incorporating cadherins of the same cell. Both dimers depend on the integrity of the same residue, Trp156. While the relative amounts of these complexes are not certain, we show here that in epithelial A-431 cells, adhesive dimers may be a prevalent form. Inactivation of the calcium-binding sites, located between successive cadherin ectodomains, drastically reduced the amount of adhesive dimers and concomitantly increased the amount of lateral dimers. A similar interdependence of adhesive and lateral dimers was observed in digitonin-permeabilized cells. In these cells, adhesive dimers immediately disassembled after lowering the Ca2+ concentration below 0.1 mM. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime. These observations suggest that cadherin-mediated adhesion is based on the dynamic cycling of E-cadherin between monomeric and adhesive dimer states.
Klingelhöfer
Jörg
J
Division of Dermatology, Washington University Medical School, St. Louis, Missouri 63110, USA.
Laur
Oscar Y
OY
Troyanovsky
Regina B
RB
Troyanovsky
Sergey M
SM
D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008856:Microscopy, Fluorescence; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
D015820:Cadherins; D004247:DNA; D002118:Calcium