Inhibitors of endocytosis prevent Wnt/Wingless signalling by reducing the level of basal ß-catenin/Armadillo.
J Cell Sci
; 127(Pt 22): 4918-26, 2014 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-25236598
ABSTRACT
A key step in the canonical Wnt signalling pathway is the inhibition of GSK3ß, which results in the accumulation of nuclear ß-catenin (also known as CTNNB1), and hence regulation of target genes. Evidence suggests that endocytosis is required for signalling, yet its role and the molecular understanding remains unclear. A recent and controversial model suggests that endocytosis contributes to Wnt signalling by causing the sequestration of the ligand-receptor complex, including LRP6 and GSK3 to multivesicular bodies (MVBs), thus preventing GSK3ß from accessing ß-catenin. Here, we use specific inhibitors (Dynasore and Dyngo-4a) to confirm the essential role of endocytosis in Wnt/Wingless signalling in human and Drosophila cells. However, we find no evidence that, in Drosophila cells or wing imaginal discs, LRP6/Arrow traffics to MVBs or that MVBs are required for Wnt/Wingless signalling. Moreover, we show that activation of signalling through chemical blockade of GSK3ß is prevented by endocytosis inhibitors, suggesting that endocytosis impacts on Wnt/Wingless signalling downstream of the ligand-receptor complex. We propose that, through an unknown mechanism, endocytosis boosts the resting pool of ß-catenin upon which GSK3ß normally acts.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endocitose
/
Proteína Wnt1
/
Beta Catenina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article