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

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.

Class I Histone Deacetylase-mediated Repression of the Proximal Promoter of the Activity-regulated Cytoskeleton-associated Protein Gene Regulates Its Response to Brain-derived Neurotrophic Factor

“…Previous studies have established that the expression of Arc is activated by neuronal activity (1,2,4,5). Consistent with this finding, we found that the expression of Arc mRNA was also increased by the direct activation of NMDA receptor (NMDAR) with exogenously added NMDA (Fig.…”

“…The gene encoding activity-regulated cytoskeleton-associated protein (Arc), 3 also known as the activity-regulated gene of 3.1 kb (Arg3.1), is an immediate early gene (IEG), the expression of which is rapidly activated in response to neuronal activity (1,2). In neurons, Arc expression is regulated by various stimuli including not only neuronal activity, but also BDNF, cAMP, and PDGF (3)(4)(5)(6).…”

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

“…Arc is classified as an immediate early gene because of its rapid induction after stimulation, but unlike c-fos, arc is not a nuclear transcription factor. Arc protein and mRNA are both specifically localized to dendrites, and arc is predicted to be involved in cytoskeletal rearrangements during the process of synaptic plasticity (Lyford et al 1995). Consistent with this interpretation, antisense inhibition of arc expression leads to impairment of the maintenance phase, but not the induction, of long-term potentiation (Guzowski et al 2000).…”

Cytoskeletal Genes Regulation by Chronic Morphine Treatment in Rat Striatum

“…The modulation of this protein in different rat brain structures by several drugs of abuse has been previously described (Ammon et al, 2003;Fosnaugh et al, 1995;Freeman et al, 2002;Kodama et al, 1998;Tan et al, 2000). The exact function of Arc is unknown but its induction and localization in dendrites and soma (Steward and Worley, 2001;Wallace et al, 1998) led to the hypothesis of its involvement in cytoskeletal rearrangements during the process of synaptic plasticity (Lyford et al, 1995). Since Arc mRNA has a short half-life (Steward and Worley, 2001), the upregulation observed here is unlikely to result from a direct action of morphine, but rather from a long-term adaptation of the dendritic network.…”