Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites

Abstract

Polyribosomal complexes beneath postsynaptic sites on dendrites provide a substrate for local translation of particular mRNAs, but the signals that target mRNAs to synapses remain to be defined. Here, we report that high frequency activation of the perforant path projections to the dentate gyrus causes newly synthesized mRNA for the immediate-early gene (IEG) Arc to localize selectively in activated dendritic segments. Newly synthesized Arc protein also accumulates in the portion of the dendrite that had been synaptically activated. The targeting of Arc mRNA was not disrupted by locally inhibiting protein synthesis, indicating that the signals for mRNA localization reside in the mRNA itself. This novel mechanism through which newly synthesized mRNA is precisely targeted to activated synapses is well suited to play a role in the enduring forms of activity-dependent synaptic modification that require protein synthesis.

A Phosphorylated Cytoplasmic Autoantigen, GW182, Associates with a Unique Population of Human mRNAs within Novel Cytoplasmic Speckles

“…It might also be that GW182 is involved in degradation of mRNA but GWBs do not colocalize with the SCF ubiquitin ligase-mediated pathway for protein degradation. Along these lines of discussion, the GWBs described in this study may be related to mRNA-associated particles described in other systems, particularly neuronal cells (Triedge et al, 1991;Miyashiro et al, 1994;Knowles et al, 1996;Martone et al, 1996;Gazzaley et al, 1997;Racca et al, 1997;Bassell et al, 1998;Steward et al, 1998). In oligodendrocytes, injected fluorescent-labeled myelin basic protein mRNA localized to granules that had a radius of 0.6 -0.8 m, contained elongation factors, rRNA and other mRNAs.…”

The Activity‐Regulated Cytoskeletal‐Associated Protein Arc Is Expressed in Different Striosome‐Matrix Patterns Following Exposure to Amphetamine and Cocaine

“…The activation of immediate-early genes has been interpreted primarily as a potential first stage in a chain of transcriptional events that could influence long-term plasticity in neurons (Morgan and Curran, 1989;Hughes and Dragunow, 1995;Kelz et al, 1999). Arc mRNA has been shown to accumulate selectively in regions of the dendritic tree that have received recent synaptic activity, providing a potential mechanism to confer synapse-specific effects of the gene (Steward et al, 1998). Our findings suggest that both cocaine and amphetamine can rapidly influence the composition of this activity-related protein in dendrites of striatal neurons, and that this influence can be exerted differentially on striosome-and matrix-based circuits of the basal ganglia.…”

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

“…In neurons, Arc expression is regulated by various stimuli including not only neuronal activity, but also BDNF, cAMP, and PDGF (3)(4)(5)(6). Arc mRNA has been detected in cell bodies, dendrites, and spines after stimulation (7,8), and the Arc protein could be synthesized locally at dendritic spines (9,10). Arc is known to be required for the endocytosis of AMPA receptors (10) and for long-term potentiation (LTP)-induced F-actin stabilization (9,11).…”