PMC

Spatial profile of sample diffusion gradients, with the rate of monomer diffusion decreasing close to the membrane (x = 0). Shown here are diffusion gradients that decrease the usual diffusion rate to 1/10 within 0.2 μm of the membrane (—) and 1/100 the usual rate within 5 μm of the membrane (···).

Steady state solution of with constant diffusion and homodimerization of cytoplasmic and bound α-catenin monomers, showing A) cytoplasmic monomer concentration and B) cytoplasmic homodimer concentration. A spatial gradient of α-catenin dimers are found in the cytoplasm when monomers bound to β- catenin are allowed to dimerize.

First possible mechanism for α-catenin homodimerization while bound to β-catenin. α-catenin, β-catenin/E-cadherin and the membrane are as described in . A. α-catenin monomers are bound to β-catenin/E-cadherin at an AJ. B. Homodimerization of E-cadherin brings α-catenin monomers into close proximity, and fluctuations in the position of α-catenin relative to β-catenin allows α-catenin to homodimerize while still bound to β-catenin. C. The α-catenin homodimer dissociates from β-catenin and diffuses into the cell.

Second possible mechanism for α-catenin homodimerization while bound to β-catenin. α-catenin, β-catenin/E-cadherin and the membrane are as described in . A. The M fragment of α-catenin monomers bound to β-catenin/E-cadherin weakly homodimerize. B. The weak α-catenin homodimer dissociates from β-catenin, allowing binding of the strong homodimerization domain. C. The weak homodimerization domain unbinds, and the strongly bound homodimer diffuses into the cell.

Sequence of events currently thought to lead to increased concentration of α-catenin homodimers near an AJ. A. α-catenin monomers (green) bind to β-catenin/E-cadherin (red) at an AJ. The plasma membrane is grey, and here the outside of the cell is below the membrane. B. α-catenin monomers are released from the AJ and diffuse into the cytoplasm. C. α-catenin monomers bind to form a homodimer that diffuses into the cell.

A) Analytic solution of at steady state and B) numeric solution of with constant diffusion and α-catenin homodimerization only in the cytoplasm, showing cytoplasmic monomer concentration (—), cytoplasmic dimer concentration (···), and membrane bound monomer concentration (●). When α-catenin bound to β-catenin can not homodimerize and there is no spatial diffusion gradient near the AJ, the cytoplasmic concentration of α-catenin monomers will never exceed the usual cytoplasmic concentration or increase the production of homodimers near an AJ.

Wheel diagram of the amino acid sequence in the α-helical coiled-coil domains of α- catenin bound to β-catenin. Shown here are the α0 (amino acids 59–81), α1 (89–116) and α2 (124–144) helices of α-catenin, which include both the β-catenin binding (54–143) and homodimerization (82–279) domains (; ; ), along with the α-catenin binding domain of β-catenin (118–141). Hydrophobic residues are shown in red. Hydrophobic residues at the e and g positions of the α 2 helix of α-catenin suggest the α/β-catenin dimer is unstable.

Numeric solution of in the presence of a diffusion gradient when both bound and cytoplasmic α-catenin monomers can homodimerize, showing A) cytoplasmic monomer concentration and B) cytoplasmic dimer concentration (membrane-bound monomer concentration not shown). When α-catenin can dimerize while bound to β-catenin, the spatial profile of cytoplasmic monomers and dimers depends on the size of the diffusion gradient and how much it slows diffusion. Shown here is a diffusion gradient that extends 1 μm into the cell and decreases monomer diffusion by a factor of 2 (—), 10 (···) and 100 (·-·-·).

Schematic of polarized epithelial cell and molecular components that make up adherens junctions (AJs). β-catenin is localized to AJs by binding to the transmembrane protein E-cadherin. The E-cadherin/β-catenin complex (red rectangle) has both intracellular and extracellular domains and crosses the membrane (thick vertical line). There is a zone of decreased diffusion near the membrane (grey area), which may be the result of crowding or non-specific binding. α-catenin monomers (green) bind to β-catenin with high affinity while α-catenin homodimers bind to polymerized actin with high affinity. In the cytoplasm, α-catenin is predominantly monomeric, suggesting the need for a mechanism to accumulate homodimers near AJs.