Activity-regulated cytoskeleton-associated protein (ARC)

Activity-regulated cytoskeleton-associated protein (ARC) is a neuron-specific, immediate-early gene protein essential for synaptic plasticity, learning, and memory formation. ARC regulates the strength and structure of synapses primarily by modulating AMPA-type glutamate receptor trafficking—facilitating endocytosis to weaken synapses and supporting dendritic spine remodeling. Its mRNA is rapidly induced and trafficked to active synapses following neuronal activity, where local translation occurs. ARC also forms unique retrovirus-like capsids, enabling cell-to-cell RNA transfer—a rare property among neuronal proteins. Disruption in ARC expression or function has been implicated in several neurological and psychiatric diseases, including Alzheimer’s disease, autism spectrum disorders, fragile X syndrome, and schizophrenia. ARC is highly conserved and lacks clear druggable domains, and to date, has not been directly targeted by therapeutics; it is best known as a molecular marker of synaptic activity and memory encoding.

Other names

ARCArcArg3.1Activity-regulated gene 3.1 protein homologARC/ARG3.1KIAA0278hArcActivity-regulated cytoskeleton-associated protein