Chronic glutamate treatment selectively modulates AMPA RNA editing and ADAR expression and activity in primary cortical neurons
Daniela Bonini
Alice Filippini
Luca La Via
Chiara Fiorentini
Fabio Fumagalli
Marina Colombi
Alessandro Barbon
10.6084/m9.figshare.1295456.v4
https://tandf.figshare.com/articles/journal_contribution/Chronic_glutamate_treatment_selectively_modulates_AMPA_RNA_editing_and_ADAR_expression_and_activity_in_primary_cortical_neurons/1295456
<div><p>Adenosine-to-inosine RNA editing is a post-transcriptional process, catalyzed by ADAR enzymes, with an important role in diversifying the number of proteins derived from a single gene. In neurons, editing of ionotropic AMPA glutamate receptors has been shown to be altered under several experimental conditions, including severe pathologies, thus highlighting the potential significance of its modulation. In this study, we treated rat primary cortical cell cultures with a sub-lethal dose of glutamate (10 μM), focusing on RNA editing and ADAR activity. We found that chronic glutamate treatment down-regulates RNA editing levels at the R/G site of GluA2-4 subunits of AMPA receptors and at the K/E site of CYFIP2. These changes are site-specific since they were not observed either for the GluA2 Q/R site or for other non-glutamatergic sites. Glutamate treatment also down-regulates the protein expression levels of both ADAR1 and ADAR2 enzymes, through a pathway that is Ca<sup>2+</sup>- and calpain-dependent. Given that AMPA receptors containing unedited subunits show a slower recovery rate from desensitization compared to those containing edited forms, the reduced editing at the R/G site may, at least in part, compensate for glutamate over-stimulation, perhaps through the reduced activation of postsynaptic receptors. In summary, our data provide direct evidence of the involvement of ADAR1 and ADAR2 activity as a possible compensatory mechanism for neuronal protection following glutamate over-stimulation.</p></div>
2015-10-10 06:32:01
modulates AMPA RNA editing
ADAR 2 activity
AMPA receptors
Chronic glutamate treatment
protein expression levels
ionotropic AMPA glutamate receptors
unedited subunits show
ADAR 1
site
CYFIP
ADAR 2 enzymes