The regulation of cell movement by the ubiquitin system.

旁轴原钙粘蛋白（Paraxial protocadherin， PAPC）在胚胎发生早期参与原肠形成细胞的运动。它首先在原肠胚早期的背缘区表达，随后局限于爪蟾和斑马鱼的近轴中胚层。利用爪蟾胚胎，我们发现PAPC在蛋白质水平上也受到调控，并且在原胚后期被降解并从轴向中胚层的质膜中排除。PAPC的调控需要多泛素化，而多泛素化依赖于进化上保守的细胞质结构域的磷酸化。我们还发现，PAPC的膜定位与低细胞运动性有关，其磷酸化/泛素化调节对正常的爪蟾原肠胚细胞运动至关重要。综上所述，我们的发现揭示了一种调节细胞粘附蛋白的新机制，该系统在脊椎动物胚胎发生中起着至关重要的作用。

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 regulated also 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 in the evolutionarily conserved cytoplasmic domain. We also show that membrane localization of PAPC is associated with low cell motility and its regulation by phosphorylation/ubiquitination is essential for normal Xenopus gastrulation cell movements. Taken together, our findings unveiled a novel mechanism of regulation of a cell adhesion protein and that this system plays a crucial role in vertebrate embryogenesis.