PUBLICATION

Phosphorylation-Dependent Ubiquitination of Paraxial Protocadherin (PAPC) Controls Gastrulation Cell Movements

Authors
Kai, M., Ueno, N., Kinoshita, N.
ID
ZDB-PUB-150113-2
Date
2015
Source
PLoS One   10: e0115111 (Journal)
Registered Authors
Ueno, Naoto
Keywords
none
MeSH Terms
  • Animals
  • Cadherins/metabolism*
  • Cell Movement/physiology*
  • Down-Regulation
  • Gastrulation/physiology*
  • Glycogen Synthase Kinase 3/metabolism
  • Phosphorylation/physiology
  • Ubiquitination/physiology*
  • Xenopus
  • Xenopus Proteins/metabolism*
PubMed
25580871 Full text @ PLoS One
Abstract
Paraxial protocadherin (PAPC) has been shown to be involved in gastrulation cell movements during early embryogenesis. It is first expressed in the dorsal marginal zone at the early gastrula stage and subsequently restricted to the paraxial mesoderm in Xenopus and zebrafish. Using Xenopus embryos, we found that PAPC is also regulated at the protein level and is degraded and excluded from the plasma membrane in the axial mesoderm by the late gastrula stage. Regulation of PAPC requires poly-ubiquitination that is dependent on phosphorylation. PAPC is phosphorylated by GKS3 in the evolutionarily conserved cytoplasmic domain, and this in turn is necessary for poly-ubiquitination by an E3 ubiquitin ligase β-TrCP. We also show that precise control of PAPC by phosphorylation/ubiquitination is essential for normal Xenopus gastrulation cell movements. Taken together, our findings unveil a novel mechanism of regulation of a cell adhesion protein and show that this system plays a crucial role in vertebrate embryogenesis.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Orthology
Engineered Foreign Genes
Mapping