Arc mediates intercellular synaptic plasticity via IRSp53-dependent extracellular vesicle biogenesis.

Ravens, A.; Sullivan, K.; Einstein, J.; Keceli, S. K.; Kicmal, T.; Tyagi, M.; Hantak, M. P.; Shepherd, T.; Stewart, A.; Lyon, K.; Dharan, A.; Gallagher, T.; Campbell, E. M.; Shepherd, J. D.

doi:10.1101/2024.01.30.578027

bioRxiv · 10.1101/2024.01.30.578027

Arc mediates intercellular synaptic plasticity via IRSp53-dependent extracellular vesicle biogenesis.

Ravens, A.·Sullivan, K.·Einstein, J.·Keceli, S. K.·Kicmal, T.·Tyagi, M.·Hantak, M. P.·Shepherd, T.·Stewart, A.·Lyon, K.·Dharan, A.·Gallagher, T.·Campbell, E. M.·Shepherd, J. D.

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Abstract

Current models of learning and memory have focused on cell-autonomous regulation of synaptic strength; however, intercellular signaling between cells in the brain is important for normal cognition. The immediate early gene Arc is a repurposed retrotransposon critical for long-term forms of synaptic plasticity and memory. Arc protein forms virus-like capsids released in extracellular vesicles (EVs) that mediate intercellular signaling of unknown function. Here, we find that long-term potentiation stimuli induce the biogenesis of Arc EVs by recruiting the I-BAR protein IRSp53, which facilitates Arc capsid assembly, trafficking, and release from actin-rich filopodial structures in dendrites. Arc EVs transfer Arc protein and mRNA to neighboring dendrites, where translation of transferred Arc mRNA induces a loss of surface AMPA-type glutamate receptors. These results show that Arc EVs mediate an intercellular form of synaptic plasticity that may be critical for memory consolidation and reveals a new neuronal EV biogenesis pathway.

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Ravens, A., Sullivan, K., Einstein, J., Keceli, S. K., Kicmal, T., Tyagi, M., Hantak, M. P., Shepherd, T., Stewart, A., Lyon, K., Dharan, A., Gallagher, T., Campbell, E. M., Shepherd, J. D.. 2024-01-30. Arc mediates intercellular synaptic plasticity via IRSp53-dependent extracellular vesicle biogenesis.. https://doi.org/10.1101/2024.01.30.578027

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