Laboratory of Systems Neurobiology and Medicine, Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Cell Rep. 2021 May 18;35(7):109130. doi: 10.1016/j.celrep.2021.109130.
Dendritic spines constitute the major compartments of excitatory post-synapses. They undergo activity-dependent enlargement, which is thought to increase the synaptic efficacy underlying learning and memory. The activity-dependent spine enlargement requires activation of signaling pathways leading to promotion of actin polymerization within the spines. However, the molecular machinery that suffices for that structural plasticity remains unclear. Here, we demonstrate that shootin1a links polymerizing actin filaments in spines with the cell-adhesion molecules N-cadherin and L1-CAM, thereby mechanically coupling the filaments to the extracellular environment. Synaptic activation enhances shootin1a-mediated actin-adhesion coupling in spines. Promotion of actin polymerization is insufficient for the plasticity; the enhanced actin-adhesion coupling is required for polymerizing actin filaments to push against the membrane for spine enlargement. By integrating cell signaling, cell adhesion, and force generation into the current model of actin-based machinery, we propose molecular machinery that is sufficient to trigger the activity-dependent spine structural plasticity.
树突棘构成兴奋性突触后的主要隔室。它们经历活动依赖性的增大，这被认为增加了学习和记忆的基础突触效能。活动依赖性的棘突增大需要激活信号通路，从而促进棘突内的肌动蛋白聚合。然而，足以实现这种结构可塑性的分子机制尚不清楚。在这里，我们证明 shootin1a 将棘突中的聚合肌动蛋白丝与细胞粘附分子 N-钙粘蛋白和 L1-CAM 连接起来，从而将丝与细胞外环境机械连接起来。突触激活增强了 shootin1a 介导的棘突中肌动蛋白-粘附的偶联。肌动蛋白聚合的促进不足以实现可塑性；增强的肌动蛋白-粘附偶联对于推动肌动蛋白丝抵抗细胞膜以增大棘突是必需的。通过将细胞信号转导、细胞粘附和力的产生整合到当前的肌动蛋白为基础的机制模型中，我们提出了足以触发活动依赖性棘突结构可塑性的分子机制。
