Activity-regulated cytoskeleton-associated
protein (
Arc/Arg3.1) is an immediate early gene, whose expression in the central nervous system is induced by specific patterns of synaptic activity.
Arc is required for the late-phase of long-term potentiation (LTP) and memory consolidation, and has been implicated in
AMPA receptor trafficking. Since
Arc's molecular function remains incompletely understood, we have determined its subcellular localization in cultured hippocampal neurons and HEK 293T cells. Fluorescence microscopy experiments revealed that both endogenous and exogenous
Arc protein was primarily found in the nucleus, where it concentrated in puncta associated with promyelocytic
leukemia (PML) bodies, proposed sites of transcriptional regulation.
Arc co-localized and interacted with the
betaIV spectrin splice variant betaSpIVSigma5, a nuclear
spectrin isoform associated with PML bodies and the nuclear matrix. A small region of
Arc containing the coiled-coil domain is also restricted to
beta-spectrin-positive puncta, while the isolated
spectrin homology domain is diffusely localized. Finally,
Arc and betaSpIVSigma5 synergistically increased the number of PML bodies. These results suggest that
Arc functions as a
spectrin-
binding protein, forming a complex that may provide a role at sites of transcriptional regulation within the nucleus.