The regulation of cell movement by the ubiquitin system.

近轴原钙粘附素(PAPC)在胚胎发育早期参与原肠形成细胞的运动。在原肠胚早期，它首先在背缘区域表达，随后在非洲爪哇和斑马鱼的中轴旁中胚层表达。利用非洲爪哇胚胎，我们发现PAPC也在蛋白质水平上受到调控，并在原肠胚后期被降解并被排除在中轴胚质膜之外。PAPC的调节需要多泛素化，这依赖于在进化上保守的细胞质区域的磷酸化。我们还发现，PAPC的膜定位与细胞的低运动性有关，它的磷酸化/泛素化调节对于非洲爪哇正常的原肠细胞运动是必不可少的。综上所述，我们的发现揭示了一种新的细胞黏附蛋白调节机制，该系统在脊椎动物胚胎发育中发挥着关键作用。

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.