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 syn-thesis 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 transla-tion 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
This work was funded by a grant from the Ministry of Economy and Competitiveness of Spain and the European Union (FEDER) (BFU2017-83375-R) to C.G. D.F.M. received an FI fellowship from Generalitat de Catalunya. F.K.M., M. Dodel, and M. Dermit were supported by a fellowship from the Medical Research Council of United Kingdom (grant ref. MR/P009417/1).