Arc ubiquitination in synaptic plasticity

The activity-regulated cytoskeleton-associated protein (Arc) is a neuron-expressed activity regulated immediate early gene (IEG) product that is essential for memory consolidation and serves as a direct readout for neural activation during learning. Arc contributes to diverse forms of synaptic plasticity mediated by the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Notably, Arc protein expression abruptly increases and then rapidly decreases following augmented network activity. A large body of work has focused on Arc transcription and translation. Far fewer studies have explored the relevance of Arc protein stability and turnover. Here, we review recent findings on the mechanisms controlling Arc degradation and discuss its contributions to AMPA receptor trafficking and synaptic plasticity.