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Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons
James Ashley1, Benjamin Cordy1, Diandra Lucia1
1Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell
|January 13, 2018
Summary
The Arc protein forms virus-like capsids that transport its own mRNA between neurons and muscles via extracellular vesicles, a process crucial for synaptic plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The Arc/Arg3.1 protein is essential for synaptic plasticity and cognition.
- Mutations in Arc are associated with autism and schizophrenia.
- Arc possesses a domain similar to retroviral Gag proteins, suggesting a role in capsid formation and RNA packaging, though its function in plasticity is unclear.
Purpose of the Study:
- To investigate the function of the Arc protein's Gag-like domain.
- To explore the mechanism of Arc-mediated mRNA transport in neurons.
- To determine the role of extracellular vesicles in synaptic plasticity.
Main Methods:
- Studied the Drosophila Arc1 protein and its interaction with darc1 mRNA.
- Investigated the formation of capsid-like structures and their loading into extracellular vesicles.
- Examined the transfer of these vesicles from motor neurons to muscles.
- Assessed the impact of disrupting vesicle transfer on synaptic plasticity.
Main Results:
- Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons.
- These structures are loaded into extracellular vesicles and transferred from motor neurons to muscles.
- Transfer depends on retrotransposon-like sequences in the darc1 mRNA's 3' untranslated region.
- Disruption of this transfer impairs synaptic plasticity.
- Cultured cells release extracellular vesicles containing retrotransposon Gag proteins and their mRNA.
Conclusions:
- Identified a novel trans-synaptic mRNA transport mechanism mediated by retrovirus-like capsids and extracellular vesicles.
- Demonstrated that Arc-mediated mRNA transport is essential for synaptic plasticity.
- Highlighted the conserved nature of this mechanism, involving both Arc and retrotransposon components.
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