Title:
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Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6
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Author:
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Vinyoles, Meritxell; Valle Pérez, Beatriz del; Curto, José; Viñas Castells, Rosa, 1985-; Alba Castellón, Lorena, 1984-; García de Herreros, Antonio; Duñach, Mireia
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Abstract:
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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. |
Abstract:
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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 ISCIII |
Subject(s):
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-Fosforilació |
Rights:
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© 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-license |
Document type:
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Article Article - Published version |
Published by:
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Elsevier
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