Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6
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 bloc...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/23820 |
| Acceso en línea: | http://hdl.handle.net/10230/23820 http://dx.doi.org/10.1016/j.molcel.2013.12.010 |
| Access Level: | acceso abierto |
| Palabra clave: | Fosforilació |
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Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6Vinyoles, MeritxellValle Pérez, Beatriz delCurto, JosuéViñas Castells, Rosa, 1985-Alba Castellón, Lorena, 1984-García de Herreros, AntonioDuñach, MireiaFosforilacióThe 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.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 ISCIIIElsevier201520152014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23820http://dx.doi.org/10.1016/j.molcel.2013.12.010reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMolecular cell. 2014;53(3):444-57info:eu-repo/grantAgreement/ES/3PN/BFU2012-31554info:eu-repo/grantAgreement/ES/3PN/SAF2010-16089© 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-licenseinfo:eu-repo/semantics/openAccessoai:recercat.cat:10230/238202026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| title |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| spellingShingle |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 Vinyoles, Meritxell Fosforilació |
| title_short |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| title_full |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| title_fullStr |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| title_full_unstemmed |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| title_sort |
Multivesicular GSK3 sequestration upon wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6 |
| dc.creator.none.fl_str_mv |
Vinyoles, Meritxell Valle Pérez, Beatriz del Curto, Josué Viñas Castells, Rosa, 1985- Alba Castellón, Lorena, 1984- García de Herreros, Antonio Duñach, Mireia |
| author |
Vinyoles, Meritxell |
| author_facet |
Vinyoles, Meritxell Valle Pérez, Beatriz del Curto, Josué Viñas Castells, Rosa, 1985- Alba Castellón, Lorena, 1984- García de Herreros, Antonio Duñach, Mireia |
| author_role |
author |
| author2 |
Valle Pérez, Beatriz del Curto, Josué Viñas Castells, Rosa, 1985- Alba Castellón, Lorena, 1984- García de Herreros, Antonio Duñach, Mireia |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
Fosforilació |
| topic |
Fosforilació |
| description |
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. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2015 2015 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/23820 http://dx.doi.org/10.1016/j.molcel.2013.12.010 |
| url |
http://hdl.handle.net/10230/23820 http://dx.doi.org/10.1016/j.molcel.2013.12.010 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Molecular cell. 2014;53(3):444-57 info:eu-repo/grantAgreement/ES/3PN/BFU2012-31554 info:eu-repo/grantAgreement/ES/3PN/SAF2010-16089 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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15,811543 |