PDF(Pubmed)
Abstract：
The Daam1 protein regulates Wnt-induced cytoskeletal changes during vertebrate gastrulation though its full mode of action and binding partners remain unresolved. Here we identify Reversion Induced LIM domain protein (RIL) as a new interacting protein of Daam1. Interaction studies uncover binding of RIL to the C-terminal actin-nucleating portion of Daam1 in a Wnt-responsive manner. Immunofluorescence studies showed subcellular localization of RIL to actin fibers and co-localization with Daam1 at the plasma membrane. RIL gain- and loss-of-function approaches in Xenopus produced severe gastrulation defects in injected embryos. Additionally, a simultaneous loss of Daam1 and RIL synergized to produce severe gastrulation defects indicating RIL and Daam1 may function in the same signaling pathway. RIL further synergizes with another novel Daam1-interacting protein, Formin Binding Protein 1 (FNBP1), to regulate gastrulation. Our studies altogether show RIL mediates Daam1-regulated non-canonical Wnt signaling that is required for vertebrate gastrulation.
摘要：
Daam1蛋白在脊椎动物原肠胚形成过程中调节Wnt诱导的细胞骨架变化，尽管其完整的作用方式和结合伴侣仍未解决。在这里，我们将逆转诱导的LIM结构域蛋白（RIL）鉴定为Daam1的新相互作用蛋白。相互作用研究揭示了RIL以Wnt响应方式与Daam1的C末端肌动蛋白成核部分的结合。免疫荧光研究表明，RIL亚细胞定位在肌动蛋白纤维上，并与Daam1共定位在质膜上。非洲爪的RIL功能增益和功能丧失方法在注射的胚胎中产生了严重的原肠胚形成缺陷。此外,Daam1和RIL的同时丢失协同产生严重的胃泌素缺陷,表明RIL和Daam1可能在相同的信号通路中起作用。RIL进一步与另一种新型Daam1相互作用蛋白协同作用，Formin结合蛋白1（FNBP1），调节胃泌素。我们的研究完全表明RIL介导Daam1调节的非规范Wnt信号传导，这是脊椎动物原肠胚形成所必需的。
