Shootin1a-mediated actin-adhesion coupling generates force to trigger structural plasticity of dendritic spines
Shootin1a-mediated actin-adhesion coupling generates force to trigger structural plasticity of dendritic spines
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DOI：
10.1016/j.celrep.2021.109130
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发表时间：
2021-05-18
期刊：
影响因子：
8.8
通讯作者：
Inagaki, Naoyuki
中科院分区：
文献类型：
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作者：
Kastian, Ria Fajarwati;Minegishi, Takunori;Inagaki, Naoyuki
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扩大，这被认为是增加学习和记忆基础的突触功效。活性依赖性棘增大需要激活信号通路，从而促进棘内的肌动蛋白聚合。然而，满足这种结构可塑性的分子机制仍然不清楚。在这里，我们证明，shootin 1a链接聚合肌动蛋白丝与细胞粘附分子N-cadherin和L1-CAM的脊柱，从而机械耦合的细丝的细胞外环境。突触激活增强了刺中shootin 1a介导的肌动蛋白粘附偶联。肌动蛋白聚合的促进不足以提供可塑性;需要增强的肌动蛋白-粘附偶联来聚合肌动蛋白丝以推压膜以使脊柱扩大。通过将细胞信号传导、细胞粘附和力生成整合到基于肌动蛋白的机制的当前模型中，我们提出了足以触发活性依赖性脊柱结构可塑性的分子机制。
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.