Reversion induced LIM domain protein (RIL) is a Daam1-interacting protein and regulator of the actin cytoskeleton during non-canonical Wnt signaling

IF 2.5 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology Pub Date : 2024-07-03 DOI:10.1016/j.ydbio.2024.06.022

Courtney Mezzacappa, Yuko Komiya, Raymond Habas

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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.

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反转诱导的 LIM 结构域蛋白（RIL）是一种与 Daam1 相互作用的蛋白，也是非典型 Wnt 信号传导过程中肌动蛋白细胞骨架的调节因子。

Daam1 蛋白调节脊椎动物胃形成过程中 Wnt 诱导的细胞骨架变化，但其全部作用模式和结合伙伴仍未确定。在这里，我们发现反转诱导的 LIM 结构域蛋白（RIL）是 Daam1 的一个新的相互作用蛋白。相互作用研究发现，RIL 以一种 Wnt 响应的方式与 Daam1 的 C 端肌动蛋白成核部分结合。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。RIL在爪蟾中的功能增益和缺失方法会导致注射胚胎出现严重的胃形成缺陷。此外，同时缺失 Daam1 和 RIL 会协同产生严重的胚胎发育缺陷，这表明 RIL 和 Daam1 可能在同一信号通路中发挥作用。RIL还与另一种与Daam1相互作用的新型蛋白--Formin Binding Protein 1（FNBP1）--协同调节胃形成。我们的研究共同表明，RIL介导Daam1调控的非经典Wnt信号传导，而这种信号传导是脊椎动物胃形成所必需的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental biology 生物-发育生物学

CiteScore

5.30

自引率

3.70%

发文量

182

审稿时长

1.5 months

期刊介绍： Developmental Biology (DB) publishes original research on mechanisms of development, differentiation, and growth in animals and plants at the molecular, cellular, genetic and evolutionary levels. Areas of particular emphasis include transcriptional control mechanisms, embryonic patterning, cell-cell interactions, growth factors and signal transduction, and regulatory hierarchies in developing plants and animals.