Syndecan-4 inhibits Wnt/ß-catenin signaling through regulation of low-density-lipoprotein receptor-related protein (LRP6) and R-spondin 3.
Int J Biochem Cell Biol
; 46: 103-12, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24275095
Regulation of Wnt signaling is crucial for embryonic development and adult homeostasis. Here we study the role of Syndecan-4 (SDC4), a cell-surface heparan sulphate proteoglycan, and Fibronectin (FN), in Wnt/ß-catenin signaling. Gain- and loss-of-function experiments in mammalian cell lines and Xenopus embryos demonstrate that SDC4 and FN inhibit Wnt/ß-catenin signaling. Epistatic and biochemical experiments show that this inhibition occurs at the cell membrane level through regulation of LRP6. R-spondin 3, a ligand that promotes canonical and non-canonical Wnt signaling, is more prone to potentiate Wnt/ß-catenin signaling when SDC4 levels are reduced, suggesting a model whereby SDC4 tunes the ability of R-spondin to modulate the different Wnt signaling pathways. Since SDC4 has been previously related to non-canonical Wnt signaling, our results also suggest that this proteoglycan can be a key component in the regulation of Wnt signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombospondinas
/
Beta Catenina
/
Sindecana-4
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Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Holanda