AUTHOR=Steward Oswald , Farris Shannon , Pirbhoy Patricia S. , Darnell Jennifer , Driesche Sarah J. Van 

TITLE=Localization and local translation of Arc/Arg3.1 mRNA at synapses: some observations and paradoxes

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=7

YEAR=2015

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2014.00101

DOI=10.3389/fnmol.2014.00101

ISSN=1662-5099

ABSTRACT=<p><italic>Arc</italic> is a unique immediate early gene whose expression is induced as synapses are being modified during learning. The uniqueness comes from the fact that newly synthesized <italic>Arc</italic> mRNA is rapidly transported throughout dendrites where it localizes near synapses that were recently activated. Here, we summarize aspects of <italic>Arc</italic> mRNA translation in dendrites <italic>in vivo</italic>, focusing especially on features of its expression that are paradoxical or that donot fit in with current models of how Arc protein operates. Findings from <italic>in vivo</italic> studies that donot quite fit include: (1) Following induction of LTP <italic>in vivo</italic>, <italic>Arc</italic> mRNA and protein localize near active synapses, but are also distributed throughout dendrites. In contrast, <italic>Arc</italic> mRNA localizes selectively near active synapses when stimulation is continued as <italic>Arc</italic> mRNA is transported into dendrites; (2) Strong induction of <italic>Arc</italic> expression as a result of a seizure does not lead to a rundown of synaptic efficacy <italic>in vivo</italic> as would be predicted by the hypothesis that high levels of Arc cause glutamate receptor endocytosis and LTD. (3) <italic>Arc</italic> protein is synthesized in the perinuclear cytoplasm rapidly after transcriptional activation, indicating that at least a pool of <italic>Arc</italic> mRNA is not translationally repressed to allow for dendritic delivery; (4) Increases in <italic>Arc</italic> mRNA in dendrites are not paralleled by increases in levels of exon junction complex (EJC) proteins. These results of studies of mRNA trafficking in neurons <italic>in vivo</italic> provide a new perspective on the possible roles of Arc in activity-dependent synaptic modifications.</p>