The cell-adhesion proteins neuroligin-3 and neuroligin-4X (NLGN3/4X) have well described roles in synapse formation. NLGN3/4X are also expressed highly during neurodevelopment. However, the role these proteins play during this period is unknown. Here we show that NLGN3/4X localized to the leading edge of growth cones where it promoted neuritogenesis in immature human neurons. Super-resolution microscopy revealed that NLGN3/4X clustering induced growth cone enlargement and influenced actin filament organization. Critically, these morphological effects were not induced by autism spectrum disorder (ASD)-associated NLGN3/4X variants. Finally, actin regulators p21-activated kinase 1 and cofilin were found to be activated by NLGN3/4X and involved in mediating the effects of these adhesion proteins on actin filaments, growth cones and neuritogenesis. These data reveal a novel role for NLGN3 and NLGN4X in the development of neuronal architecture, which may be altered in the presence of ASD-associated variants.

中文翻译：

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Neuroligin-3 和 neuroligin-4X 形成纳米级簇并调节生长锥组织和大小

细胞粘附蛋白 neuroligin-3 和 neuroligin-4X (NLGN3/4X) 在突触形成中具有很好的作用。NLGN3/4X 在神经发育过程中也有高表达。然而，这些蛋白质在此期间发挥的作用尚不清楚。在这里，我们表明 NLGN3/4X 定位于生长锥的前缘，在那里它促进未成熟人类神经元的神经发生。超分辨率显微镜显示 NLGN3/4X 聚类诱导生长锥扩大并影响肌动蛋白丝组织。至关重要的是，这些形态学效应不是由自闭症谱系障碍 (ASD) 相关的 NLGN3/4X 变异引起的。最后，发现肌动蛋白调节剂 p21 激活激酶 1 和 cofilin 被 NLGN3/4X 激活，并参与介导这些粘附蛋白对肌动蛋白丝、生长锥和神经发生的影响。