WAVE调节复合体与Boc相互作用，是Shh介导的轴突导向所必需的。
The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance.
作者信息
Balekoglu Nursen, Michaud Jean-Francois, Sauvé Rachelle, Ayinde Kehinde S, Lin Sichun, Liu Yijun, Kramer Daniel A, Zhang Kaiyue, Steffen Anika, Stradal Theresia, Angers Stephane, Chen Baoyu, Yam Patricia T, Charron Frédéric
机构信息
Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada.
Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 2B4, Canada.
出版信息
iScience. 2024 Nov 6;27(12):111333. doi: 10.1016/j.isci.2024.111333. eCollection 2024 Dec 20.
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 and 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.
在发育过程中， Sonic Hedgehog（Shh）将脊髓连合神经元的轴突吸引至底板。Shh介导的连合轴突吸引需要受体Boc。Boc如何响应Shh调节生长锥中的细胞骨架变化尚不完全清楚。为了鉴定Boc在Shh介导的轴突导向中的效应器，我们使用生物素邻近标记法（BioID）筛选与Boc邻近的蛋白质。排名靠前的包括WAVE调节复合物（WRC）的成员，该复合物在Rac1下游起作用以促进肌动蛋白细胞骨架组装。因此，我们假设WRC对Shh介导的生长锥转向很重要。通过生化和细胞分析，我们发现Boc直接与WRC相互作用，并且这种相互作用可以在活细胞中发生。此外，我们发现，在连合神经元中敲低WRC的两个亚基和会损害轴突向Shh梯度的吸引。我们的结果表明，WRC是Shh介导的轴突吸引所必需的。
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