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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Viral-like mechanisms of extracellular vesicle biogenesis in neurons

on the September 24, 2018
11:30

Seminar by Jason Shepherd (University of Utah, USA)

The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation. Purified Arc capsids are endocytosed and are able to transfer Arc mRNA into the cytoplasm of neurons. These results show that Arcexhibits similar molecular properties to retroviral Gag proteins. Evolutionary analysis indicates that Arc is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are also ancestors to retroviruses. These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system.


References:
  • Pastuzyn ED, Day CE, Kearns RB, Kyrke-Smith M, Taibi AV, McCormick J, Yoder N, Belnap DM, Erlendsson S, Morado DR, Briggs JAG, Feschotte C, Shepherd JD.
    The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer.
    Cell. 2018 Jan 11;172(1-2):275-288
  • Ashley J., Cordy B., Lucia D., Fradkin L.G., Budnik V., Thomson T.
    Retrovirus-like Gag protein Arc1 binds RNA and traffics across synaptic boutons.
    Cell. 2018; 172: 262-274

Host: Rémy Sadoul.

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