Exosomal muscle derived miRNA transfer regulates local protein synthesis at the presynaptic motor neuron

Neurons are highly polarized cells with long axons that can extend to more than one meter in human adults. In order to properly develop, survive and maintain normal function, the neuron depends on local protein synthesis events. This essential process occurs in neuronal axons far from the cell body and nucleus, allows the neuron to respond specifically to external cues and various stimulations, and thus requires tight regulation. The molecular mechanism that regulates spatial and temporal protein local synthesis in the axon remains largely unknown. As growing evidence suggest that secreted miRNA-containing exosomes play a role in intercellular communication, it is possible that such mechanism is key in this regulation. Here, using cutting edge TIRF microscopy, cellular and biochemical approaches, we demonstrate miRNA transfer via exosomes from muscles to axons. Our working hypothesis is that miRNAs are secreted and transported from muscle cells to neuronal axons via exosomes in order to regulate axonal local protein synthesis events, which are essential to neuronal function. Alterations in this process can lead to neurodegeneration as occur in ALS. We will seek to define those miRNA factors and understand the mechanism involved in this intercellular communication.