Iioka Hidekazu, Iemura Shun-ichiro, Natsume Tohru, Kinoshita Noriyuki
Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan.
Nat Cell Biol. 2007 Jul;9(7):813-21. doi: 10.1038/ncb1607. Epub 2007 Jun 10.
Gastrulation movements are critical for establishing the three germ layers and the architecture of vertebrate embryos. During Xenopus laevis gastrulation, mesodermal tissue migrates on the blastocoel roof and elongates along the antero-posterior axis. During this process, cells in the dorsal mesoderm are polarized and intercalate with each other, which is defined as convergent extension and is known to be regulated by the non-canonical Wnt pathway. Here, we show that paxillin plays an essential role in this process. Paxillin is a focal-adhesion associated protein implicated in the regulation of actin cytoskeletal organization and cell motility, but its role in Xenopus embryogenesis has not yet been clarified. We demonstrate that the Wnt pathway controls the ubiquitination and stability of paxillin, and that this regulatory mechanism is essential for convergent extension movements. We identified a RING finger protein XRNF185, which physically binds to paxillin and the proteasome. XRNF185 destabilizes paxillin at focal adhesions and promotes mesodermal cell migration during convergent extension. We propose a mechanism to regulate gastrulation movements that involves paxillin ubiquitination and stability controlled by Wnt signalling.
原肠胚形成运动对于建立三个胚层和脊椎动物胚胎的结构至关重要。在非洲爪蟾原肠胚形成过程中，中胚层组织在囊胚腔顶迁移并沿前后轴伸长。在此过程中，背侧中胚层中的细胞发生极化并相互插入，这被定义为汇聚延伸，已知其受非经典Wnt信号通路调控。在此，我们表明桩蛋白在此过程中发挥着重要作用。桩蛋白是一种与粘着斑相关的蛋白质，参与肌动蛋白细胞骨架组织和细胞运动的调控，但其在非洲爪蟾胚胎发育中的作用尚未阐明。我们证明Wnt信号通路控制桩蛋白的泛素化和稳定性，并且这种调控机制对于汇聚延伸运动至关重要。我们鉴定出一种环状结构域蛋白XRNF185，它与桩蛋白和蛋白酶体发生物理结合。XRNF185使粘着斑处的桩蛋白不稳定，并在汇聚延伸过程中促进中胚层细胞迁移。我们提出一种调控原肠胚形成运动的机制，该机制涉及由Wnt信号控制的桩蛋白泛素化和稳定性。
