Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6
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- dc.contributor.author Vinyoles, Meritxellca
- dc.contributor.author Valle Pérez, Beatriz delca
- dc.contributor.author Curto, Josuéca
- dc.contributor.author Viñas Castells, Rosa, 1985-ca
- dc.contributor.author Alba Castellón, Lorena, 1984-ca
- dc.contributor.author García de Herreros, Antonioca
- dc.contributor.author Duñach, Mireiaca
- dc.date.accessioned 2015-06-15T07:19:08Z
- dc.date.available 2015-06-15T07:19:08Z
- dc.date.issued 2014ca
- dc.description.abstract The Wnt canonical ligands elicit the activation of β-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 of the 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 do not completely prevent, the β-catenin upregulation caused by Wnt3a. These results, besides elucidating how GSK3 is sequestered into MVBs, support this mechanism as cause of β-catenin stabilization by Wnt.en
- dc.description.sponsorship This work was funded by grants from the Ministerio de Economía (BFU2012-31554 to M.D. and SAF2010-16089 to A.G.H.) and Fundació La Marató de TV3 (120130) to M.D. and A.G.H. Support from Fundación Científica de la Asociación Española contra el Cáncer, ISCIII/FEDER (RD12/0036/005) and Generalitat de Catalunya (2009SGR867) is also appreciated. M.V. and L.A.-C. were recipients of predoctoral fellowships from FPI, and R.V.-C. was a recipient of a fellowship from ISCIIIen
- dc.format.mimetype application/pdfca
- dc.identifier.citation Vinyoles M, DelValle-Párez B, Curto J, Viñas-Castells R, Alba-Castellón L, Garcia de Herreros A et al. Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6. Molecular cell. 2014;53(3):444-57. DOI: 10.1016/j.molcel.2013.12.010ca
- dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2013.12.010
- dc.identifier.issn 1097-2765ca
- dc.identifier.uri http://hdl.handle.net/10230/23820
- dc.language.iso engca
- dc.publisher Elsevierca
- dc.relation.ispartof Molecular cell. 2014;53(3):444-57
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-31554
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-16089
- dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.molcel.2013.12.010 that appeared in the journal Molecular cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseen
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Fosforilacióca
- dc.title Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6en
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca