Deconstructing the cadherin-catenin-actin complex.
Spatial and functional organization of cells in tissues is determined by cell-cell adhesion, thought to be initiated through trans-interactions between extracellular domains of the cadherin family of adhesion proteins, and strengthened by linkage to the actin cytoskeleton. Prevailing dogma is that cadherins are linked to the actin cytoskeleton through beta-catenin and alpha-catenin, although the quaternary complex has never been demonstrated. We test this hypothesis and find that alpha-catenin does not interact with actin filaments and the E-cadherin-beta-catenin complex simultaneously, even in the presence of the actin binding proteins vinculin and alpha-actinin, either in solution or on isolated cadherin-containing membranes. Direct analysis in polarized cells shows that mobilities of E-cadherin, beta-catenin, and alpha-catenin are similar, regardless of the dynamic state of actin assembly, whereas actin and several actin binding proteins have higher mobilities. These results suggest that the linkage between the cadherin-catenin complex and actin filaments is more dynamic than previously appreciated.
Yamada
Soichiro
S
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pokutta
Sabine
S
Drees
Frauke
F
Weis
William I
WI
Nelson
W James
WJ
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015638:Cytochalasin D / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D047630:Depsipeptides / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D046912:Multiprotein Complexes; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D000970:Antineoplastic Agents; D015820:Cadherins; D047630:Depsipeptides; D005456:Fluorescent Dyes; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D019384:Nucleic Acid Synthesis Inhibitors; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin; D051176:beta Catenin; C057531:jasplakinolide; D016596:Vinculin; D015638:Cytochalasin D