eEF1A2 controls local translation and actin dynamics in structural synaptic plasticity

Mendoza, M. B.; Gutierrez, S.; Ortiz, R.; Moreno, D. F.; Dermit, M.; Dodel, M.; Rebollo, E.; Bosch, M.; Mardakheh, F. K.; Gallego, C.

doi:10.1101/2020.10.20.346858

bioRxiv · 10.1101/2020.10.20.346858

eEF1A2 controls local translation and actin dynamics in structural synaptic plasticity

Mendoza, M. B.·Gutierrez, S.·Ortiz, R.·Moreno, D. F.·Dermit, M.·Dodel, M.·Rebollo, E.·Bosch, M.·Mardakheh, F. K.·Gallego, C.

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Abstract

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.

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Mendoza, M. B., Gutierrez, S., Ortiz, R., Moreno, D. F., Dermit, M., Dodel, M., Rebollo, E., Bosch, M., Mardakheh, F. K., Gallego, C.. 2020-10-20. eEF1A2 controls local translation and actin dynamics in structural synaptic plasticity. https://doi.org/10.1101/2020.10.20.346858

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