RAB8B Is Required for Activity and Caveolar Endocytosis of LRP6

被引：48

作者：

Demir, Kubilay ^{[1
]}

Kirsch, Nadine ^{[2
]}

Beretta, Carlo A. ^{[1
]}

Erdmann, Gerrit ^{[1
]}

Ingelfinger, Dierk ^{[1
]}

Moro, Enrico ^{[3
]}

Argenton, Francesco ^{[4
]}

Carl, Matthias ^{[1
]}

Niehrs, Christof ^{[2
,5
]}

Boutros, Michael ^{[1
]}

机构：

[1] Heidelberg Univ, Div Signaling & Funct Genom, German Canc Res Ctr DKFZ, Dept Cell & Mol Biol,Med Fac Mannheim, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Div Mol Embryol, D-69120 Heidelberg, Germany

[3] Univ Padua, Dept Biomed Sci, I-35131 Padua, Italy

[4] Univ Padua, Dept Biol, I-35131 Padua, Italy

[5] Inst Mol Biol, D-55128 Mainz, Germany

来源：

CELL REPORTS | 2013年 / 4卷 / 06期

关键词：

BETA-CATENIN; WNT; PHOSPHORYLATION; ACTIVATION; ENDOSOMES; PROTEINS; REVEALS; IMAGE;

D O I：

10.1016/j.celrep.2013.08.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wnt/beta-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/beta-catenin signaling. RAB8B depletion reduces LRP6 activity, beta-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/beta-catenin signaling through regulation of LRP6 activity and endocytosis.

引用

页码：1224 / 1234

页数：11

共 38 条

[1]

Abramoff M.D., 2004, Biophotonics International, V11, P36

[2] Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor [J].