The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-06 DOI:10.1016/j.isci.2024.111333

Nursen Balekoglu , Jean-Francois Michaud , Rachelle Sauvé , Kehinde S. Ayinde , Sichun Lin , Yijun Liu , Daniel A. Kramer , Kaiyue Zhang , Anika Steffen , Theresia Stradal , Stephane Angers , Baoyu Chen , Patricia T. Yam , Frédéric Charron

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Abstract

During development, Shh attracts axons of spinal cord commissural neurons to the floor plate. Shh-mediated attraction of commissural axons requires the receptor Boc. How Boc regulates cytoskeletal changes in growth cones in response to Shh is not fully understood. To identify effectors of Boc in Shh-mediated axon guidance, we used BioID to screen for proteins in proximity to Boc. Top hits included members of the WAVE regulatory complex (WRC), which acts downstream of Rac1 to promote actin cytoskeleton assembly. Therefore, we hypothesized that the WRC is important for Shh-mediated growth cone turning. Using biochemical and cellular assays, we found that Boc directly interacts with the WRC and that this interaction can occur in live cells. Moreover, we found that knockdown of Nckap1 and Cyfip1/2, two subunits of the WRC, in commissural neurons, impairs axon attraction toward a Shh gradient. Our results demonstrate that the WRC is required for Shh-mediated axon attraction.

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WAVE 调控复合物与 Boc 相互作用，是 Shh 介导的轴突导向所必需的

在发育过程中，Shh 会将脊髓神经元的轴突吸引到底板上。Shh 介导的神经轴突吸引需要受体 Boc。Boc 如何调节生长锥的细胞骨架变化以对 Shh 作出反应，目前还不完全清楚。为了鉴定 Boc 在 Shh 介导的轴突导向中的效应因子，我们使用 BioID 筛选了与 Boc 接近的蛋白质。点击率最高的包括波调节复合体（WRC）的成员，该复合体作用于 Rac1 的下游，促进肌动蛋白细胞骨架的组装。因此，我们推测 WRC 对 Shh 介导的生长锥转动非常重要。通过生化和细胞实验，我们发现 Boc 可直接与 WRC 相互作用，而且这种作用可在活细胞中发生。此外，我们还发现，在神经元中敲除 WRC 的两个亚基 Nckap1 和 Cyfip1/2，会影响轴突向 Shh 梯度的吸引。我们的研究结果表明，WRC 是 Shh 介导的轴突吸引所必需的。

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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