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.

Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk’s subjugate SG dynamics to a conserved hysteretic switch.

Synaptic plasticity involves structural modifications in dendritic spines. Increasing evidence suggests that structural plasticity is modulated by local protein synthesis and actin remodeling in a synapsis-specific manner. However, the precise molecular mechanisms connecting synaptic stimulation to these processes in dendritic spines are still unclear. In the present study, we demonstrate that the configuration of phosphorylation sites in eEF1A2, an essential translation elongation factor in neurons, is a key modulator of structural plasticity in dendritic spines. A mutant that cannot be phosphorylated stimulates translation but reduces actin dynamics and spine density. By contrast, the phosphomimetic variant loosens its association with F-actin and becomes inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers a transient dissociation of eEF1A2 from its GEF protein in dendritic spines, in a phospho-dependent manner. We propose that eEF1A2 establishes a crosstalk mechanism that coordinates local translation and actin dynamics during spine remodeling

Stress granules are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge on their regulation and functional relevance is still incipient.Here we describe a mutual-inhibition interplay between stress granules and Cdc28, the budding yeast Cdk. Amongst Cdc28 interactors acting as negative modulators of Start we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdks subjugate SG dynamics to a conserved hysteretic switch.