Arc: building a bridge from viruses to memory

Arc (activity-regulated cytoskeleton-associated protein) is a neuron-specific immediate early gene that is required for enduring forms of synaptic plasticity and memory in the mammalian brain. Arc expression is highly dynamic, and tightly regulated by neuronal activity and experience. Local translation of Arc protein at synapses is critical for synaptic plasticity, which is mediated by Arc-dependent trafficking of AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-type glutamate receptors. To date, few structural or biophysical properties of Arc protein have been investigated. Recent studies, including that of Myrum et al. published in the 468:1 issue of the Biochemical Journal, now shed light on some intriguing biophysical properties of Arc. These findings show that Arc contains large N- and C-terminal domains around a flexible linker region and that purified Arc protein is capable of self-oligomerization. Intriguingly, these domains show homology with the viral capsid protein found in the gag polypeptide of most retroviruses. These studies provide insight into how Arc may regulate multiple critical cell biological processes in neurons and reveals unanticipated biology that resembles viral trafficking in cells.