Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility
Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility
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DOI：
10.1038/ncb1607
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发表时间：
2007-07-01
影响因子：
21.3
通讯作者：
Kinoshita, Noriyuki
中科院分区：
文献类型：
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作者：
Iioka, Hidekazu;Iemura, Shun-ichiro;Kinoshita, Noriyuki
原肠胚形成运动对于脊椎动物胚胎的三个胚层和结构的建立是至关重要的。在非洲爪蟾原肠胚形成期间，中胚层组织在囊胚腔顶部迁移并沿前后轴沿着伸长（1），（2）。在此过程中，背侧中胚层中的细胞被极化并相互插入，这被定义为会聚延伸，并且已知由非经典Wnt途径调节（3 - 5）。在这里，我们表明桩蛋白在这个过程中起着至关重要的作用。桩蛋白是一种与肌动蛋白细胞骨架组织和细胞运动调节有关的局灶性粘附相关蛋白（6），7，但其在非洲爪蟾胚胎发生中的作用尚未阐明。我们证明了Wnt通路控制着桩蛋白的泛素化和稳定性，并且这种调节机制对于聚合延伸运动是必不可少的。我们鉴定了一种RING指蛋白XRNF185，它与桩蛋白和蛋白酶体物理结合。XRNF 185使粘着斑处的桩蛋白不稳定，并促进会聚伸展期间的中胚层细胞迁移。我们提出了一种机制来调节原肠胚运动，涉及桩蛋白泛素化和稳定性控制的Wnt信号。
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(1),(2). 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(3-5). 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(6),7, 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.