Beta-catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to beta-catenin.
beta-Catenin plays a central role in the establishment and regulation of adherens junctions because it interacts with E-cadherin and, through alpha-catenin, with the actin cytoskeleton. beta-Catenin is composed of three domains: a central armadillo repeat domain and two N- and C-terminal tails. The C-tail interacts with the armadillo domain and limits its ability to bind E-cadherin and other cofactors. The two beta-catenin tails are mutually inter-regulated because the C-tail is also necessary for binding of the N-tail to the armadillo domain. Moreover, the N-tail restricts the interaction of the C-tail with the central domain. Depletion of either of the two tails has consequences for the binding of factors at the other end: deletion of the C-tail increases alpha-catenin binding, whereas deletion of the N-tail blocks E-cadherin interaction to the armadillo repeats. As an effect of the interconnection of the tails, the association of alpha-catenin and E-cadherin to beta-catenin is interdependent. Thus, binding of alpha-catenin to the N-tail, through conformational changes that affect the C-tail, facilitates the association of E-cadherin. These results indicate that different cofactors of beta-catenin bind coordinately to this protein and indicate how the two terminal ends of beta-catenin exquisitely modulate intermolecular binding within junctional complexes.
Castaño
Julio
J
Unitat de Biofisica, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Raurell
Imma
I
Piedra
José A
JA
Miravet
Susana
S
Duñach
Mireia
M
García de Herreros
Antonio
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001665:Binding Sites; D015820:Cadherins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D051176:beta Catenin
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015534:Trans-Activators; D051176:beta Catenin