Rem2 in the bullfrog (Rana catesbeiana): Patterns of expression within the central nervous system and brain expression at different ontogenetic stages

DeRocher, Megan M.; Armaly, Faris H.; Lepore, Cara J.; Hollis, David M.

doi:10.1016/j.gene.2014.02.030

Cited by 10 publications

(14 citation statements)

References 57 publications

(114 reference statements)

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“…This pattern is consistent with the patterns of expression of rem2 isoforms in the trout using Taqman probes (Hollis et al, 2012). The significantly high levels of rem2 seen in the cerebrum, as well as the near absence of observed rem2 expression in the cerebellum are consistent with the pattern seen in the brain of an amphibian (DeRocher et al, 2014). Thus, the overall pattern of relative expression levels of rem2 across the major subdivisions within the anamniotic central nervous system appears to be conserved.…”

Section: Resultssupporting

confidence: 81%

“…Comparatively, the lack of observable r em2 mRNA-labeled cells in the rainbow trout cerebellum, in addition to its near lack expression via rtPCR, is consistent with another anamniotic vertebrate, the bullfrog (DeRocher et al 2014). This is in sharp contrast to the mouse cerebellum, which has higher levels of relative rem2 expression than the midbrain, brainstem, and spinal cord (Liput et al, 2016).…”

Section: Resultssupporting

confidence: 58%

“…Rem2 has been well-characterized and appears conserved as it has been isolated in different classes of vertebrates including mammals and fish (Klein et al, 2002; Edel et al, 2010b; Hollis et al, 2012; DeRocher et al 2014). Because Rem2 regulates voltage-gated calcium channels (VGCCs), it enables Ca 2+ to influence neurotransmitter release.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it also influences cell division, differentiation, migration, and death, of which, tremendous discrepancies between the mammalian and fish brain exist (Zupanc, 1999; Ferretti, 2011). Rem2, unlike other RGK members, is characterized by having high expression levels in neural tissue relative to other tissues, which is conserved between mammals and fish, as well as amphibians (Finlin et al, 2000; Hollis et al 2012; DeRocher et al, 2014). However, comparative data regarding the specific regional distribution of rem2 in the central nervous system between the vertebrate classes is lacking.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Downs

Scholles

Hollis

2016

Journal of Chemical Neuroanatomy

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Rem2 is member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras superfamily of GTP binding proteins known to influence Ca2+ entry into the cell. In addition, Rem2, which is found at high levels in the vertebrate brain, is also implicated in cell proliferation and synapse formation. Though the specific, regional localization of Rem2 in the adult mammalian central nervous system has been well-described, such information is lacking in other vertebrates. We sought to localize rem2 gene expression in the central nervous system. Because Rem2 is involved in neuronal processes where differences in the capacities between adults of the different vertebrate classes exist, we sought to localize the rem2 gene in the central nervous system of an adult anamniotic vertebrate, the rainbow trout (Oncorhynchus mykiss). In situ hybridization using a digoxigenin (DIG)-labeled RNA probe was used to identify the regional distribution of rem2 expression throughout the trout central nervous system, while real-time polymerase chain reaction (rtPCR) further supported these findings. Based on in situ hybridization, the regional distribution of rem2 occurred within each major subdivision of the brain and included large populations of rem2 expressing cells in the dorsal telencephalon of the cerebrum, the internal cellular layer of the olfactory bulb, and the optic tectum of the midbrain. In contrast, no rem2 expressing cells were resolved within the cerebellum. These results were corroborated by rtPCR, where differential rem2 expression occurred between the major subdivisions assayed with the highest levels being found in the cerebrum, while it was nearly absent in the cerebellum. These data indicate that rem2 gene expression is broadly distributed and likely influences diverse functions in the adult fish central nervous system.

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Section: Resultssupporting

confidence: 81%

Section: Resultssupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Downs

Scholles

Hollis

2016

Journal of Chemical Neuroanatomy

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

Liput

Davis

et al. 2016

Sci Rep

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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.

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Evolutionary analysis of mammalian Rem2, a member of the RGK (Rem, Rem2, Rad, and Gem/Kir) family of small GTPases, reveals the role of selection and epistasis in shaping protein functional constraints

Lucaci,

Brew,

Pond

et al. 2023

Preprint

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Rad And Gem-Like GTP-Binding Protein 2 (Rem2), is a member of the RGK family of Ras-like GTPases and has been identified in various mammalian species.Rem2has been implicated in Huntington’s disease and Long QT Syndrome and is highly expressed in the brain and in endocrine cells. In this study, we examined the evolutionary history ofRem2across mammals, focusing on the role of purifying selection and epistasis in shaping its sequence and structure. In our analysis ofRem2sequences across 175 mammalian species, we found evidence for strong purifying selection in 70% of non-invariant codon sites of the protein, characteristic of essential proteins that play critical roles in biological processes and is consistent withRem2’s role in the regulation of neuronal development and function. We inferred epistatic effects in 49 pairs of coevolving codon sites inRem2,some of which are predicted to have deleterious effects on human health. Additionally, we reconstructed the ancestral evolutionary history of mammalianRem2using protein structure prediction of extinct and extant sequences. This analysis revealed the dynamics of how substitutions that change the genetic distance of Rem2 can impact protein structure in variable regions while maintaining core functional mechanisms. By understanding the selective pressures, protein- and genetic-interactions that have shaped the sequence and structure of the Rem2 protein, we may gain a stronger understanding of its biological and functional constraints.

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Rem2 in the bullfrog (Rana catesbeiana): Patterns of expression within the central nervous system and brain expression at different ontogenetic stages

Cited by 10 publications

References 57 publications

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

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

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

Evolutionary analysis of mammalian Rem2, a member of the RGK (Rem, Rem2, Rad, and Gem/Kir) family of small GTPases, reveals the role of selection and epistasis in shaping protein functional constraints

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