The regulator of G protein signaling type 10 (RGS10) modulates Gαi/o signaling by means of its GTPase accelerating activity and is abundantly expressed in brain and in immune tissues. To elucidate RGS10 function in the nervous system, we mapped RGS10 protein in rat and mouse brain using light microscopic (LM) and electron microscopic (EM) immunohistochemical techniques. The LM showed that RGS10-like immunoreactivity (LIR) labels all cellular subcompartments of neurons and microglia, including their nuclei. There were several differences between RGS10-LIR distributions in rat and mouse, the most striking of which were the far denser immunoreactivity in rat dentate gyrus and dorsal raphe. The EM analysis corroborated and extended our findings from LM. Thus, EM confirmed the presence of dense RGS10-LIR in the euchromatin compartment of nuclei. The EM analysis also resolved dense staining on terminals at symmetric synapses onto pyramidal cell somata. Dual immunofluorescence showed that forebrain interneurons densely labeled with RGS10-LIR partially colocalized with parvalbumin-LIR. Dual-labeling histochemistry in caudoputamen demonstrated that densely labeled striatal cells were biased to the indirect-projecting output pathway. Dual-labeling immunofluorescence also showed that densely labeled RGS10-LIR cells in the dentate gyrus subgranular zone were not proliferating but that newly born cells could differentiate to express RGS10-LIR. Taken together, these data support a role for RGS10 in diverse processes that include modulation of pre- and postsynaptic G-protein signaling. Moreover, enrichment of RGS10 in transcriptionally active regions of the nucleus suggests an unforeseen role of RGS10 in modulating gene expression.
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