Vesicular Rps6 released by astrocytes regulate local translation and enhance synaptic markers in neurons

Abstract

In neurons, like in any other cell, their function often relies on the fine tuning of their protein levels, which is achieved by the balance between protein synthesis and turnover. Defects in protein homeostasis frequently leads to neuronal dysfunction and neurological disorders. Given their extreme morphological complexity and high compartmentalization, neurons highly depend on the asymmetrical distribution of their proteome. The common belief is that proteins that sustain axonal, dendritic and synaptic functions are synthesized in the soma and then transported to distal neuronal compartments. However, there is a complementary mechanism by which the mRNAs, and not the proteins, are transported to distal subneuronal domains, and once they reach their destination they are locally translated. Although once considered heretical, local translation (or local protein synthesis) is now widely accepted by the scientific community. Nonetheless there is one question that remains largely unexplored in the field and that is whether local translation in dendrites, axons and synapses is fully regulated by the neuron itself or if non-neuronal cells (e.g. glia) can modulate this mechanism in a non-cell-autonomous manner. Here we show that astroglia regulates local protein synthesis and enhances synaptic markers by releasing extracellular vesicles (EVs) containing ribosomal protein Rps6. To our knowledge this is the first report that directly demonstrates glial control of local translation in neurons through EV-mediated glia-to-neuron communication.