The amino- and carboxyl-terminal tails of (beta)-catenin reduce its affinity for desmoglein 2.
beta-catenin and plakoglobin are members of the armadillo family of proteins and were first identified as components of intercellular adhering junctions. In the adherens junction beta-catenin and plakoglobin serve to link classical cadherins to the actin-based cytoskeleton. In the desmosome plakoglobin links the desmosomal cadherins, the desmogleins and the desmocollins, to the intermediate filament cytoskeleton. beta-catenin is not a component of the desmosome. Previously we have shown that the central armadillo repeat region of plakoglobin is the site for desmosomal cadherin binding. We hypothesized that the unique amino- and/or carboxyl-terminal ends of beta-catenin may regulate its exclusion from the desmosomal plaque. To test this hypothesis we used chimeras between beta-catenin and plakoglobin to identify domain(s) that modulate association with desmoglein 2. Chimeric constructs, each capable of associating with classical cadherins, were assayed for association with the desmosomal cadherin desmoglein 2. Addition of either the N- or C-terminal tail of beta-catenin to the armadillo repeats of plakoglobin did not interfere with desmoglein 2 association. However, when both beta-catenin amino terminus and carboxyl terminus were added to the plakoglobin armadillo repeats, association with desmoglein 2 was diminished. Removal of the first 26 amino acids from this construct restored association. We show evidence for direct protein-protein interactions between the amino- and carboxyl-terminal tails of beta-catenin and propose that a sequence in the first 26 amino acids of beta-catenin along with its carboxyl-terminal tail decrease its affinity for desmoglein and prevent its inclusion in the desmosome.
Wahl JK3rd
Department of Biology, University of Toledo, Toledo, OH 43606, USA.
Nieset
J E
JE
Sacco-Bubulya
P A
PA
Sadler
T M
TM
Johnson
K R
KR
Wheelock
M J
MJ
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D051187:Desmocollins; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry; D006801:Humans; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D051185:gamma Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; C495314:DSG2 protein, human; D051187:Desmocollins; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin