Multivesicular GSK3 Sequestration upon Wnt Signaling Is Controlled by p120-Catenin/Cadherin Interaction with LRP5/6

Meritxell Vinyoles, Beatriz DelValle-Pérez, Josué Curto, Rosa Viñas-Castells, Lorena Alba-Castellón, Antonio García de Herreros, Mireia Duñach

Research output: Contribution to journalArticleResearchpeer-review

79 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)444-457
JournalMolecular Cell
Volume53
DOIs
Publication statusPublished - 6 Feb 2014

Fingerprint

Dive into the research topics of 'Multivesicular GSK3 Sequestration upon Wnt Signaling Is Controlled by p120-Catenin/Cadherin Interaction with LRP5/6'. Together they form a unique fingerprint.

Cite this