mRNA Trafficking in the Nervous System: A Key Mechanism of the Involvement of Activity-Regulated Cytoskeleton-Associated Protein (Arc) in Synaptic Plasticity

Figure 3

Regulation of the transcription of the activity-regulated cytoskeleton-associated protein (Arc) gene. Some known and putative pathways are presented only. Basic low-level Arc transcription can be further decreased by the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Arc transcription is promoted by signaling through the NMDAR (N-methyl-D-aspartate receptor), mGluR (group 1 metabotropic glutamate receptor), TrkB (tropomycin-receptor kinase B), and mAChR (muscarinic acetylcholine receptor) signaling pathways through the interaction with several downstream kinases, including ERK (extracellular-signal-regulated kinase), PKA (protein kinase A), and PKC (protein kinase C). ERK increases Arc transcription through its coactivator TCF (ternary complex factor) binding to SRE (serum response element) in the Arc promoter. ERK may also increase Arc transcription through its Zeste-like factor directly interacting with ZRE (Zeste-like response element) in the Arc promoter. The transcription start site (TSS) and direction of transcription are marked by the bold arrow above the Arc gene. Ach: acetylcholine; BDNF: brain-derived neurotrophic factor.