Neuron-derived extracellular vesicles contain synaptic proteins, promote spine formation, activate TrkB-mediated signalling and preserve neuronal complexity

神经元衍生的细胞外囊泡含有突触蛋白,促进脊柱形成,激活 TrkB 介导的信号传导并保持神经元的复杂性

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作者:Julia Solana-Balaguer, Genís Campoy-Campos, Núria Martín-Flores, Leticia Pérez-Sisqués, Laia Sitjà-Roqueta, Melike Kucukerden, Ana Gámez-Valero, Albert Coll-Manzano, Eulàlia Martí, Esther Pérez-Navarro, Jordi Alberch, Jordi Soriano, Mercè Masana, Cristina Malagelada

Abstract

Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such as bioactive miRNAs, proteins and lipids. EVs are key players in the functioning of the central nervous system (CNS) by influencing synaptic events and modulating recipient neurons. However, the specific role of neuron-to-neuron communication via EVs is still not well understood. Here, we provide evidence that primary neurons uptake neuron-derived EVs in the soma, dendrites, and even in the dendritic spines, and carry synaptic proteins. Neuron-derived EVs increased spine density and promoted the phosphorylation of Akt and ribosomal protein S6 (RPS6), via TrkB-signalling, without impairing the neuronal network activity. Strikingly, EVs exerted a trophic effect on challenged nutrient-deprived neurons. Altogether, our results place EVs in the spotlight for synaptic plasticity modulation as well as a possible therapeutic tool to fight neurodegeneration.

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