Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia

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.

Localization of rem2 in the central nervous system of the adult rainbow trout (Oncorhynchus mykiss)

“…The high levels of rem2 expression in areas of the forebrain of the rainbow trout is similar to that seen in the mouse (Liput et al 2016). Like the mouse, where rtPCR data indicated the highest relative rem2 expression levels in the striatum and nucleus accumbens, large populations of densely labeled rem2 mRNA expressing cells were observed in the subpallial regions of the vd and vc.…”

“…This included the dp, dl-v, and dl-d (homologous to the dentate gyrus). In the mouse hippocampus, specifically hippocampal formation CA3, there is a very high level of rem2 expression relative to other brain regions (Liput et al, 2016). Another contributing factor to the high levels of rem2 expression seen in the rainbow trout cerebrum would be the large population of rem2 mRNA-labeled cells observed in the dm, which is considered homologous to the mammalian amygdala (Ganz et al, 2015).…”

“…Another contributing factor to the high levels of rem2 expression seen in the rainbow trout cerebrum would be the large population of rem2 mRNA-labeled cells observed in the dm, which is considered homologous to the mammalian amygdala (Ganz et al, 2015). In the mouse, the amygdala also has a significant level of rem2 expression (Liput et al, 2016). …”

“…In the rainbow trout, the dc possessed a large population of rem2 mRNA-labeled cells, which were some of the most intensely labeled in the entire central nervous system. In contrast, the cortex of the mouse indicates an exceptionally low level of rem2 expression (Liput et al, 2016). This discrepancy may either be due to different roles of rem2 across vertebrates within the region or due to functional differences between the homologous regions.…”

“…However, comparative data regarding the specific regional distribution of rem2 in the central nervous system between the vertebrate classes is lacking. In mammals, expression of rem2 was described in the forebrain (Becker et al, 2008), however, recent work has shown that, not only does the distribution of rem2 occur throughout the major subdivisions of the mammalian central nervous system, but there are profound differences in its level of expression between specific brain areas (Liput et al, 2016). While the distribution of rem2 in the major subdivisions of the central nervous system has been examined in both developing and adult fish (Edel et al, 2010b; Hollis et al, 2012), as well as in an adult amphibian (DeRocher et al, 2014), the specific regional localization of rem2 throughout the adult anamniotic vertebrate central nervous system has yet to be examined.…”