RAB8B is required for activity and caveolar endocytosis of LRP6.
Cell Rep
; 4(6): 1224-34, 2013 Sep 26.
Article
de En
| MEDLINE
| ID: mdl-24035388
ABSTRACT
Wnt/ß-catenin signaling plays an important role in embryonic development and adult tissue homeostasis. When Wnt ligands bind to the receptor complex, LRP5/6 coreceptors are activated by phosphorylation and concomitantly endocytosed. In vertebrates, Wnt ligands induce caveolin-dependent endocytosis of LRP6 to relay signal downstream, whereas antagonists such as Dickkopf promote clathrin-dependent endocytosis, leading to inhibition. However, little is known about how LRP6 is directed to different internalization mechanisms, and how caveolin-dependent endocytosis is mediated. In an RNAi screen, we identified the Rab GTPase RAB8B as being required for Wnt/ß-catenin signaling. RAB8B depletion reduces LRP6 activity, ß-catenin accumulation, and induction of Wnt target genes, whereas RAB8B overexpression promotes LRP6 activity and internalization and rescues inhibition of caveolar endocytosis. In Xenopus laevis and Danio rerio, RAB8B morphants show lower Wnt activity during embryonic development. Our results implicate RAB8B as an essential evolutionary conserved component of Wnt/ß-catenin signaling through regulation of LRP6 activity and endocytosis.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines oncogènes
/
Endocytose
/
Protéines de type Wingless
/
Protéine-6 apparentée au récepteur des LDL
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cell Rep
Année:
2013
Type de document:
Article
Pays d'affiliation:
Allemagne