Abstract
Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein primarily expressed in mouse pyramidal neurons of hippocampal area CA2 where it regulates synaptic plasticity important for learning and memory. However, very little is known about RGS14 protein expression in the primate brain. Here, we validate the specificity of a new polyclonal RGS14 antibody that recognizes not only full-length RGS14 protein in primate, but also lower molecular weight forms of RGS14 protein matching previously predicted human splice variants. These putative RGS14 variants along with full-length RGS14 are expressed in the primate striatum. By contrast, only full-length RGS14 is expressed in hippocampus, and shorter variants are completely absent in rodent brain. We report that RGS14 protein immunoreactivity is found both pre- and postsynaptically in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra, and amygdala in adult rhesus monkeys. A similar cellular expression pattern of RGS14 in the monkey striatum and hippocampus was further confirmed in humans. Our electron microscopy data show for the first time that RGS14 immunostaining localizes within nuclei of striatal neurons in monkeys. Taken together, these findings suggest new pre- and postsynaptic regulatory functions of RGS14 and RGS14 variants, specific to the primate brain, and provide evidence for unconventional roles of RGS14 in the nuclei of striatal neurons potentially important for human neurophysiology and disease.
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Acknowledgements
We would like to acknowledge and thank Marla Gearing, Deborah Cooper, and Susan Jenkins for their very valuable assistance with processing tissue and their continuous guidance. We would also like to acknowledge the Emory Alzheimer’s Disease Research Center for providing the human tissue (AG025688), and the Neuropathology/Histochemistry Core of the Emory NINDS Neurosciences Core Facility (P30 NS055077) for processing the human tissue. This work was supported, in whole or in part, by the National Institutes of Health grants 5R01NS037112 and 1R21 NS087488 (both awarded to JRH), Yerkes National Primate Research Center NIH base grant P51OD011132, and F31NS098648 (awarded to KJG). Additionally, both KJG and KES were supported by NIH training Grant T32 GM008602.
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Co-first authors: Katherine E. Squires, Kyle J. Gerber.
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Squires, K.E., Gerber, K.J., Pare, JF. et al. Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain. Brain Struct Funct 223, 233–253 (2018). https://doi.org/10.1007/s00429-017-1487-y
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DOI: https://doi.org/10.1007/s00429-017-1487-y