Synaptic plasticity involves structural modifications in dendritic spines that are modulated by local protein synthesis and actin remodeling. Here, we investigated the molecular mechanisms that connect synaptic stimulation to these processes. We found that the phosphorylation of isoform-specific sites in eEF1A2—an essential translation elongation factor in neurons—is a key modulator of structural plasticity in dendritic spines. Expression of a nonphosphorylatable eEF1A2 mutant stimulated mRNA translation but reduced actin dynamics and spine density. By contrast, a phosphomimetic eEF1A2 mutant exhibited decreased association with F-actin and was inactive as a translation elongation factor. Activation of metabotropic glutamate receptor signaling triggered transient dissociation of eEF1A2 from its regulatory guanine exchange factor (GEF) protein in dendritic spines in a phosphorylation-dependent manner. We propose that eEF1A2 establishes a cross-talk mechanism that coordinates translation and actin dynamics during spine remodeling.

突触可塑性涉及树突棘的结构修饰，这些修饰受局部蛋白质合成和肌动蛋白重塑的调节。在这里，我们研究了将突触刺激与这些过程联系起来的分子机制。我们发现 eEF1A2 中亚型特异性位点的磷酸化（神经元中一种重要的翻译延伸因子）是树突棘结构可塑性的关键调节剂。非磷酸化 eEF1A2 突变体的表达刺激了 mRNA 翻译，但降低了肌动蛋白动力学和脊柱密度。相比之下，拟磷化 eEF1A2 突变体与 F-肌动蛋白的关联降低，并且作为翻译延伸因子没有活性。代谢型谷氨酸受体信号传导的激活触发了 eEF1A2 与其在树突棘中的调节性鸟嘌呤交换因子 (GEF) 蛋白以磷酸化依赖性方式瞬时解离。我们建议 eEF1A2 建立一个串扰机制，在脊柱重塑过程中协调翻译和肌动蛋白动力学。