Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites

TLDR

Neuronal activity is an essential stimulus for induction of plasticity and normal development of the CNS. Using differential cloning, the authors identified a novel immediate‑early gene (IEG) cDNA that is rapidly induced by neuronal activity, and sequence analysis revealed alpha‑spectrin homology with the protein coprecipitating with F‑actin. Arc mRNA and protein are enriched in dendrites and the subplasmalemmal cortex, colocalize with actin, and likely contribute to activity‑dependent dendritic plasticity.

Abstract

Neuronal activity is an essential stimulus for induction of plasticity and normal development of the CNS. We have used differential cloning techniques to identify a novel immediate-early gene (IEG) cDNA that is rapidly induced in neurons by activity in models of adult and developmental plasticity. Both the mRNA and the encoded protein are enriched in neuronal dendrites. Analysis of the deduced amino acid sequence indicates a region of homology with alpha-spectrin, and the full-length protein, prepared by in vitro transcription/translation, coprecipitates with F-actin. Confocal microscopy of the native protein in hippocampal neurons demonstrates that the IEG-encoded protein is enriched in the subplasmalemmal cortex of the cell body and dendrites and thus colocalizes with the actin cytoskeletal matrix. Accordingly, we have termed the gene and encoded protein Arc (activity-regulated cytoskeleton-associated protein). Our observations suggest that Arc may play a role in activity-dependent plasticity of dendrites.