The arcane relationship between Arc’s virus-like properties and its role in AMPA receptor endocytosis.

Abstract

Arc is a critical player in synaptic plasticity and is essential for long term memory consolidation. The most well-established method by which Arc influences synaptic plasticity is by enabling the endocytosis of AMPA receptors. Recently it was shown that Arc originates from the Ty3/Gypsy retrotransposon family. Similar to many endogenous retroviruses (ERVs) Arc was shown to bind and package its own mRNA into virus like particles (VLPs). These particles were shown to release from cells and ‘Infect’ neighboring neurons, where they were observed to undergo activity-dependent translation. Indeed the virus-like properties of Arc is an emerging topic of interest. However, the relationship between the protein’s ability to bind and sequester AMPA receptors and to oligomerize and form capsids remains unclear. Here we review factors influencing the oligomerization of Arc and propose that capsid formation and receptor endocytosis are two competing processes which may be balanced by post translational modifications. We compare Arc to other endogenous retroviral proteins and propose a model for the virus-like life cycle of Arc. This is important for understanding the mechanism behind this type of intercellular communication and how it could affect synaptic plasticity.