The canonical Wnt signalling pathway is a key regulator of cell proliferation. When an extracellular Wnt ligand is present, β-catenin – which is otherwise phosphorylated by the axin-containing destruction complex and subsequently degraded – accumulates in the nucleus and activates target genes. By contrast, axin redistributes to the plasma membrane, which has led to the suggestion that axin relocation is the key event that halts β-catenin destruction. Now, however, Maarten Fornerod and colleagues () describe a new step in the nuclear translocation of β-catenin. The authors show that, upon Wnt3a stimulation, unphosphorylated β-catenin is recruited to the plasma membrane (the protein can be detected at the membrane in E-cadherin–/– cells, indicating that it is distinct from E-cadherin-bound, junctional β-catenin). The redistribution of β-catenin to the membrane is an early event in the Wnt response and β-catenin colocalises with the Wnt co-receptor LRP6, and with axin and APC (another component of the destruction complex). Moreover, the association of β-catenin with LRP6 increases its transcriptional activity. These results imply that β-catenin is activated in a Wnt-receptor complex at the plasma membrane, before translocating to the nucleus.
