PDF(Pubmed)
Abstract：
The Formin protein Daam1 is required for Wnt-induced cytoskeletal changes during gastrulation, though how it accomplishes this remains unresolved. Here we report the characterization of Formin Binding Protein 1 (FNBP1) as a binding partner of Daam1. The interaction of Daam1 with FNBP1 and its domains required for this interaction were delineated. Immunofluorescence studies showed FNBP1 co-localizes with Daam1, and is an integral component of the actin cytoskeletal complex that is responsive to Wnt stimulation. Specifically, FNBP1 can induce intracellular tubule-like structures and localize to focal adhesions suggesting a role for FNBP1 in cell migration. Functional FNBP1 studies in Xenopus embryos uncover a critical role for FNBP1 in regulating vertebrate gastrulation. Additionally, suboptimal doses of Daam1 and FNBP1 synergize to produce severe gastrulation defects, indicating FNBP1 and Daam1 may function within the same signaling pathway. These results together show FNBP1 is an integral component of Daam1-regulated non-canonical Wnt signaling required for vertebrate gastrulation.
摘要：
Formin蛋白Daam1是胃泌素过程中Wnt诱导的细胞骨架变化所必需的，尽管它如何实现这一目标仍未解决。在这里，我们报告了Formin结合蛋白1（FNBP1）作为Daam1的结合配偶体的表征。描绘了Daam1与FNBP1的相互作用及其该相互作用所需的结构域。免疫荧光研究显示FNBP1与Daam1共定位,并且是响应于Wnt刺激的肌动蛋白细胞骨架复合物的组成部分。具体来说,FNBP1可以诱导细胞内小管样结构并定位为粘着斑，表明FNBP1在细胞迁移中的作用。非洲爪狼胚胎中的功能性FNBP1研究揭示了FNBP1在调节脊椎动物原肠胚形成中的关键作用。此外,Daam1和FNBP1的次优剂量协同产生严重的胃泌素缺陷，表明FNBP1和Daam1可能在同一信号通路内发挥作用。这些结果共同显示FNBP1是脊椎动物原肠胚形成所需的Daam1调节的非规范Wnt信号传导的组成部分。
