Abstract
Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology.
Highlights
Most of the research on RGK proteins has focused on the molecular mechanisms of RGK-HVA calcium channel interactions in heterologous expression systems or have relied on molecular approaches such as in vitro RNA interference
This work is essential to our understanding of the RGK protein family, there are only a few studies exploring the role of these proteins in the physiology of intact model organisms
We sought to extend the available information on Rem[2] mRNA and protein expression in the nervous system
Summary
Most of the research on RGK proteins has focused on the molecular mechanisms of RGK-HVA calcium channel interactions in heterologous expression systems or have relied on molecular approaches such as in vitro RNA interference. There is a paucity of information on which tissues and cell-types express RGK proteins. One study found relatively high expression of Rem[2] transcript in the striatum and extended amygdala using in situ hybridization[18], but did not examine Rem[2] protein expression, identify cell-type expression, or determine subcellular localization. Such information is necessary for elucidating the functions of Rem[2] in nervous system physiology. Rem[2] mRNA was detectable in most nervous system tissues examined, in the CNS Rem[2] mRNA and protein was enriched in nuclei of the basal ganglia. Rem[2] mRNA expression peaked at PND7-14, a time frame when dendritic spines and synapses are rapidly developing, implicating Rem[2] in these events in vivo
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