PUBLICATION

RAB8B is required for activity and caveolar endocytosis of LRP6

Authors
Demir, K., Kirsch, N., Beretta, C.A., Erdmann, G., Ingelfinger, D., Moro, E., Argenton, F., Carl, M., Niehrs, C., and Boutros, M.
ID
ZDB-PUB-131125-1
Date
2013
Source
Cell Reports   4(6): 1224-1234 (Journal)
Registered Authors
Argenton, Francesco, Beretta, Carlo, Carl, Matthias, Moro, Enrico
Keywords
none
MeSH Terms
  • Zebrafish
  • Animals
  • HEK293 Cells
  • Signal Transduction
  • Humans
  • HeLa Cells
  • Transfection
  • Oncogene Proteins/genetics
  • Oncogene Proteins/metabolism*
  • Endocytosis/physiology*
  • Wnt Proteins/genetics*
  • Wnt Proteins/metabolism
  • Phosphorylation
  • Xenopus
  • Low Density Lipoprotein Receptor-Related Protein-6/genetics
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism*
(all 16)
PubMed
24035388 Full text @ Cell Rep.
Abstract

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

Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ia4TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    rab8bMO1-rab8bMRPHLNO
    rab8bMO2-rab8bMRPHLNO
    1 - 2 of 2
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    Fish
    1 - 3 of 3
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
    1 - 1 of 1
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    Mapping
    No data available