The Wnt canonical ligands elicit the activation ofβ-catenin transcriptional activity, a response dependent on, but not limited to, β-catenin stabilization through the inhibition of GSK3 activity. Two mechanisms have been proposed for this inhibition, one dependent on the binding and subsequent block of GSK3 to LRP5/6 Wnt coreceptor and another one on its sequestration into multivesicular bodies (MVBs). Here we report that internalization ofthe GSK3-containing Wnt-signalosome complex into MVBs is dependent on the dissociation of p120-catenin/cadherin from this complex. Disruption of cadherin-LRP5/6 interaction is controlled by cadherin phosphorylation and requires the previous separation of p120-catenin; thus, p120-catenin and cadherin mutants unable to dissociate from the complex block GSK3 sequestration into MVBs.These mutants substantially inhibit, but donot completely prevent, the β-catenin upregulationcaused by Wnt3a. These results, besides elucidating how GSK3 is sequestered into MVBs, support this mechanism as cause of β-catenin stabilization by Wnt. © 2014 Elsevier Inc.
Vinyoles, M., DelValle-Pérez, B., Curto, J., Viñas-Castells, R., Alba-Castellón, L., García de Herreros, A., & Duñach, M. (2014). Multivesicular GSK3 Sequestration upon Wnt Signaling Is Controlled by p120-Catenin/Cadherin Interaction with LRP5/6. Molecular Cell, 53(3), 444–457. https://doi.org/10.1016/j.molcel.2013.12.010