Description:

Jason D. Shepherd, Ph.D.

Jon M. Huntsman Presidential Endowed Chair

Chan Zuckerberg Initiative Ben Barres Investigator

Associate Professor 

Departments of Neurobiology, Biochemistry, and Ophthalmology & Visual Sciences

University of Utah

Abstract:

Learning and experience induces a specific set of genes that mediate long-lasting maintenance of synaptic strength, epigenetic alterations of chromatin, and neuronal homeostasis. One key activity-dependent gene, Arc, is a critical mediator of long-lasting synaptic plasticity and memory. Recently, we identified a new type of intercellular communication mediated by Arc that could be central to its function. We unexpectedly observed that purified Arc protein spontaneously forms virus-like capsids and determined that the Arc gene originated from an ancient family of retrotransposons. We posited that if Arc forms capsids, perhaps other functional aspects of retroviruses have also been retained. We found that purified Arc capsids encapsulate RNA, including Arc mRNA. Endogenous Arc from the brain also associates with its own mRNA and is released in extracellular vesicles (EVs) from primary cultured neurons. Strikingly, Arc-containing EVs can transfer Arc mRNA into Arc knock-out neurons. Thus, Arc has retained biochemical functions of the ancestral retrovirus Gag protein. These findings raise the possibility that Arc-dependent intercellular communication might underlie its function in learning and memory. In this talk, I'll describe new data suggesting Arc mediates a novel form of intercellular synaptic plasticity.