Dl. Rimm et al., ALPHA(1)(E)-CATENIN IS AN ACTIN-BINDING AND ACTIN-BUNDLING PROTEIN MEDIATING THE ATTACHMENT OF F-ACTIN TO THE MEMBRANE ADHESION COMPLEX, Proceedings of the National Academy of Sciences of the United Statesof America, 92(19), 1995, pp. 8813-8817
Calcium-dependent homotypic cell-cell adhesion, mediated by molecules
such as E-cadherin, guides the establishment of classical epithelial c
ell polarity and contributes to the control of migration, growth, and
differentiation, These actions involve additional proteins, including
alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage
to the cortical actin cytoskeleton, The molecular basis for these inte
ractions and their hierarchy of interaction remain controversial. We d
emonstrate a direct interaction between F-actin and alpha(E)-catenin,
an activity not shared by either the cytoplasmic domain of E-cadherin
or beta-catenin. Sedimentation assays and direct visualization by tran
smission electron microscopy reveal that alpha(1)(E)-catenin binds and
bundles F-actin in vitro with micromolar affinity at a catenin/G-acti
n monomer ratio of approximate to 1:7 (mol/mol), Recombinant human bet
a-catenin can simultaneously bind to the alpha-catenin/actin complex b
ut does not bind actin directly. Recombinant fragments encompassing th
e amino-terminal 228 residues of alpha(1)(E)-catenin or the carboxyl-t
erminal 447 residues individually bind actin in cosedimentation assays
with reduced affinity compared with the full-length protein, and neit
her fragment bundles actin, Except for similarities to vinculin, neith
er region contains sequences homologous to established actin-binding p
roteins, Collectively these data indicate that alpha(1)(E)-catenin is
a novel actin binding and -bundling protein and support a model in whi
ch alpha(1)(E)-catenin is responsible for organizing and tethering act
in filaments at the zones of E-cadherin-mediated cell-cell contact.