title: Phosphorylation-dependent ubiquitination of paraxial protocadherin (PAPC) controls gastrulation cell movements.
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.
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji-cho, Okazaki, Aichi 444-8585, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Kai
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji-cho, Okazaki, Aichi 444-8585, Japan; Department of Molecular Biomechanics, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji-cho, Okazaki, Aichi 444-8585, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji-cho, Okazaki, Aichi 444-8585, Japan; Department of Molecular Biomechanics, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji-cho, Okazaki, Aichi 444-8585, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D015536:Down-Regulation; D054262:Gastrulation / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D000091363:Protocadherins; D054875:Ubiquitination / Q000502:physiology*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; C117635:Pcdh8 protein, Xenopus; D000091363:Protocadherins; D029867:Xenopus Proteins; D038362:Glycogen Synthase Kinase 3