PUBLICATION

Lypd6 Enhances Wnt/beta-Catenin Signaling by Promoting Lrp6 Phosphorylation in Raft Plasma Membrane Domains

Authors
Özhan, G., Sezgin, E., Wehner, D., Pfister, A.S., Kühl, S.J., Kagermeier-Schenk, B., Kühl, M., Schwille, P., and Weidinger, G.
ID
ZDB-PUB-130905-3
Date
2013
Source
Developmental Cell   26(4): 331-345 (Journal)
Registered Authors
Kagermeier-Schenk, Birgit, Özhan, Günes, Wehner, Daniel, Weidinger, Gilbert
Keywords
none
MeSH Terms
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Wnt Signaling Pathway*/genetics
  • Body Patterning/genetics
  • Xenopus/embryology
  • Xenopus/genetics
  • Xenopus/metabolism*
  • Protein Transport
  • Phosphorylation
  • Mice
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Embryo, Nonmammalian/metabolism
  • Glycosylphosphatidylinositols/metabolism
  • Protein Binding
  • Transcription, Genetic
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism*
  • Receptors, Wnt/metabolism
  • Models, Biological
  • Antigens, Ly/metabolism*
  • Humans
  • Membrane Microdomains/metabolism*
  • Molecular Sequence Data
  • Gene Expression Regulation, Developmental
  • Neural Plate/embryology
  • Neural Plate/metabolism
  • HEK293 Cells
  • Animals
(all 31)
PubMed
23987510 Full text @ Dev. Cell
Abstract

Wnt/β-catenin signaling plays critical roles during embryogenesis, tissue homeostasis, and regeneration. How Wnt-receptor complex activity is regulated is not yet fully understood. Here, we identify the Ly6 family protein LY6/PLAUR domain-containing 6 (Lypd6) as a positive feedback regulator of Wnt/β-catenin signaling. lypd6 enhances Wnt signaling in zebrafish and Xenopus embryos and in mammalian cells, and it is required for wnt8-mediated patterning of the mesoderm and neuroectoderm during zebrafish gastrulation. Lypd6 is GPI anchored to the plasma membrane and physically interacts with the Wnt receptor Frizzled8 and the coreceptor Lrp6. Biophysical and biochemical evidence indicates that Lypd6 preferentially localizes to raft membrane domains, where Lrp6 is phosphorylated upon Wnt stimulation. lypd6 knockdown or mislocalization of the Lypd6 protein to nonraft membrane domains shifts Lrp6 phosphorylation to these domains and inhibits Wnt signaling. Thus, Lypd6 appears to control Lrp6 activation specifically in membrane rafts, which is essential for downstream signaling.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ia5TgTransgenic Insertion
    w32TgTransgenic Insertion
      w34TgTransgenic Insertion
        w35TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          lypd6MO1-lypd6MRPHLNO
          wnt8aMO1-wnt8aMRPHLNO
          wnt8aMO2-wnt8aMRPHLNO
          1 - 3 of 3
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          Fish
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          mCherryEFGmCherry
          YFPEFGYFP
          1 - 3 of 3
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          Mapping
          No data available