The elongation factor eEF1A2 controls translation and actin dynamics in dendritic spines

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.

Automated summary

Phosphorylation of eEF1A2 plays a key role in synaptic plasticity in dendritic spines. Nonphosphorylatable eEF1A2 mutant stimulates mRNA translation but reduces actin dynamics and spine density, while phosphomimetic eEF1A2 mutant is inactive as a translation elongation factor. Activation of metabotropic glutamate receptor signaling triggers transient dissociation of eEF1A2 from its regulatory guanine exchange factor (GEF) protein in a phosphorylation-dependent manner.