LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation.
Cell Signal
; 26(5): 1068-74, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24412751
ABSTRACT
Canonical Wnt/ß-catenin signaling pathway plays important roles in multiple aspects of cellular responses in development and diseases. It is currently thought that Wnt receptor Frizzled (Frz) exists separately to Wnt coreceptors LRP5 and LRP6 (LRP5/6), and that Wnt-Frz-LRP5/6 triple complex formation bridged by Wnt ligand is needed for canonical pathway activation. We recently showed that Frz and LRP5/6 interact with each other in the absence of Wnt ligand binding and this interaction maintains the Frz-LRP5/6 complex in an inactive state. Here, we further show that Wnt ligand stimulation induces conformational change of the Frz-LRP6 complex and leads to hexamer formation containing the core LDLR domain-mediated LRP6 homodimer that is stabilized by two pairs of Wnt3a and Frz8, that is, Wnt3a-Frz8-LRP6-LRP6-Frz8-Wnt3a. This LDLR-mediated LRP6 dimerization is essential for robust canonical Wnt pathway activation. Our study thus suggests a previously unrecognized mode of receptor interaction in Wnt signal initiation.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Proteína Wnt3A
/
Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article