Intercellular Communication in Long Term Memory

Arc forms virus-like capsids via a conserved retroviral Gag capsid domain. (A) EM images of purified Arc protein. Insets show Arc capsids. (B) Arc mRNA is locally translated in dendrites, and Arc protein forms capsids which encapsulate RNAs and proteins that are released, mediating transfer to neighboring cells.

How can cells in the brain retain information for years, even though most proteins turn over in minutes to days? The neuronal gene Arc is critical for transducing experience and learning into long-lasting changes in the brain.

Shepherd and colleagues found that the Arc gene is derived from a family of retrotransposons, and that the Arc protein can self-assemble into virus-like capsids that are released from neurons in membrane-enclosed vesicles that transfer RNA and proteins cell-to-cell. These findings open a new area of investigation in the cell biology of cell-to-cell communication and mechanisms of brain plasticity by uncovering a novel intercellular communication pathway that resembles retrovirus biology.

Jason Shepherd, PhD. and Elissa Pastuzyn, Ph.D.


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The neuronal gene Arc encodes a repurposed retrotransposon Gag protein that mediates intercellular RNA transfer. 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. Cell. 2018 Jan;172(1-2):275.

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