Autism- and epilepsy-associated EEF1A2 mutations lead to translational dysfunction and altered actin bundling.

ABSTRACT: Protein synthesis is a fundamental cellular process in neurons that is essential for synaptic plasticity and memory consolidation. Here, we describe our investigations of a neuron- and muscle-specific translation factor, eukaryotic Elongation Factor 1a2 (eEF1A2), which when mutated in patients results in autism, epilepsy, and intellectual disability. We characterize three EEF1A2 patient mutations, G70S, E122K, and D252H, and demonstrate that all three mutations decrease de novo protein synthesis and elongation rates in HEK293 cells. In mouse cortical neurons, the EEF1A2 mutations not only decrease de novo protein synthesis but also alter neuronal morphology, regardless of endogenous levels of eEF1A2, indicating that the mutations act via a toxic ga

SUBMITTER: Mohamed MS 

PROVIDER: S-EPMC10515156 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature