Synaptic activity mediates information storage and memory consolidation in the brain and requires a fast de novo synthesis of mRNAs in the nucleus and
proteins in synapses. Intracellular localization of a
protein can be achieved by
mRNA trafficking and localized translation. Activity-regulated cytoskeleton-associated
protein (
Arc) is a master regulator of synaptic plasticity and plays an important role in controlling large signaling networks implicated in learning, memory consolidation, and behavior. Transcription of the
Arc gene may be induced by a short behavioral event, resulting in synaptic activation.
Arc mRNA is exported into the cytoplasm and can be trafficked into the dendrite of an activated synapse where it is docked and translated. The structure of
Arc is similar to the viral GAG (group-specific
antigen)
protein, and phylogenic analysis suggests that
Arc may originate from the family of Ty3/Gypsy
retrotransposons. Therefore,
Arc might evolve through "domestication" of retroviruses.
Arc can form a capsid-like structure that encapsulates a retrovirus-like sentence in the 3'-UTR (
untranslated region) of
Arc mRNA. Such complex can be loaded into extracellular vesicles and transported to other neurons or muscle cells carrying not only genetic information but also regulatory signals within neuronal networks. Therefore,
Arc mRNA inter- and intramolecular trafficking is essential for the modulation of synaptic activity required for memory consolidation and cognitive functions. Recent studies with single-molecule imaging in live neurons confirmed and extended the role of
Arc mRNA trafficking in synaptic plasticity.