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Séminaire - Jason ShepherdViral-like mechanisms of intercellular signaling in the nervous system

Abstract :

"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. We recently discovered thats Arc self-assembles into viral-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.
Evolutionary analysis indicates that Arc is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are also ancestral to retroviruses such as HIV.
These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system."

Selected publications

Cell. 2018 Jan 11;172(1-2):275-288.e18. doi: 10.1016/j.cell.2017.12.024. 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.

Semin Cell Dev Biol. 2018 May;77:73-78. doi: 10.1016/j.semcdb.2017.09.029. Epub 2017 Sep 24. Arc - An endogenous neuronal retrovirus? Shepherd JD.

Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9182-9187. doi: 10.1073/pnas.1700866114. Epub 2017 Aug 8. Arc restores juvenile plasticity in adult mouse visual cortex. Jenks KR, Kim T, Pastuzyn ED, Okuno H,, Taibi AV, Bito H, Bear MF, Shepherd JD.

Front Mol Neurosci. 2017 Jul 28;10:234. doi: 10.3389/fnmol.2017.00234. eCollection 2017. Activity-Dependent Arc Expression and Homeostatic Synaptic Plasticity Are Altered in Neurons from a Mouse Model of Angelman Syndrome.
Pastuzyn ED, Shepherd JD.