Postnatal developmental expression of regulator of G protein signaling 14 (RGS14) in the mouse brain

Abstract

Regulator of G Protein Signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and MAPK signaling pathways. In the adult mouse brain, RGS14 mRNA and protein are found almost exclusively in hippocampal CA2 neurons. We have shown that RGS14 is a natural suppressor of CA2 synaptic plasticity and hippocampal-dependent learning and memory. However, the protein distribution and spatiotemporal expression patterns of RGS14 in mouse brain during postnatal development are unknown. Here, using a newly characterized monoclonal anti-RGS14 antibody, we demonstrate that RGS14 protein immunoreactivity is undetectable at birth (P0) with very low mRNA expression in the brain. However, RGS14 protein and mRNA are upregulated during early postnatal development, with protein first detected at P7, and both increasing over time until reaching highest sustained levels throughout adulthood. Our immunoperoxidase data demonstrate that RGS14 protein is expressed in regions outside of hippocampal CA2 during development including the primary olfactory areas, the anterior olfactory nucleus and piriform cortex, and the olfactory associated orbital and entorhinal cortices. RGS14 is also transiently expressed in neocortical layers II/III and V during postnatal development. Finally, we show that RGS14 protein is first detected in the hippocampus at P7 with strongest immunoreactivity in CA2 and fasciola cinerea and sporadic immunoreactivity in CA1; labeling intensity in hippocampus increases until adulthood. These results show that RGS14 mRNA and protein are upregulated throughout postnatal mouse development, and RGS14 protein exhibits a dynamic localization pattern that is enriched in hippocampus and primary olfactory cortex in the adult mouse brain.

Integration of G Protein α (Gα) Signaling by the Regulator of G Protein Signaling 14 (RGS14)

“…By contrast, in the absence of G␣ i1 -GDP, RGS14 remains cytosolic yet can be recruited by activated G␣ o -AlF 4 Ϫ to the plasma membrane via the RGS domain. Together with previous observations of RGS14 localization in brain and CA2 neurons (8,9), our findings here suggest that RGS14 exists as distinct cellular subpopulations, either bound to the plasma membrane in complex with G␣ i -GDP or recruited from the cytosol to the plasma membrane by active G␣-GTP followed by capture of the G␣-GDP resulting from GAP activity.…”

“…Our previous studies have indicated that native RGS14 exists both in the soluble (cytosolic) and particulate (membrane) fractions of brain lysates (7), and is localized diffusely within the soma, dendrites, and spines and at the postsynaptic density in CA2 neurons of mouse brain (8,9). We also have shown that recombinant RGS14 can bind inactive G␣ subunits at the plasma membrane through the GPR motif (13).…”

“…Our previous research has revealed that RGS14 (regulator of G protein signaling 14), a member of the R12 subfamily of RGS proteins, is highly expressed in the brain (7,8) and is a natural suppressor of CA2 hippocampal synaptic plasticity and learning and memory (9,10). RGS14 has a unique domain structure with an N-terminal RGS domain and a C-terminal G protein regulatory (GPR; also known as GoLoco) motif.…”

Enhanced longevity and metabolism by brown adipose tissue with disruption of the regulator of G protein signaling 14

“…RGS14 is a complex RGS family member that contains a canonical RGS domain, a tandem (R1 and R2) Ras/Rap binding domain (Kiel et al., 2005; Wohlgemuth et al., 2005), as well as a GoLoco/GPR motif. Most prior work on RGS14 focused on its effects on embryonic development and on the visual cortex and central nervous system (Evans, Lee, Smith & Hepler, 2014; Lee et al., 2010; Lopez‐Aranda et al., 2009; Shu, Ramineni & Hepler, 2010; Vellano, Brown, Blumer & Hepler, 2013). The role of BAT in RGS14 KO and its ability to enhance lifespan and improve metabolism, the focus of the present investigation, have never been explored.…”

Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity

“…Overall, the status of RGS2 as an immediate early gene highly expressed in multiple types of neurons throughout the brain allows it to play a unique role in modulating G protein signaling at the synapse. (Cho et al, 2000;Traver et al, 2000;Hollinger et al, 2001) Hippocampus (Traver et al, 2000;Lee et al, 2010;Evans et al, 2014) Somatodendritic compartment of CA2 pyramidal neurons including the PSD (Lee et al, 2010) Suppresses LTP in CA2 hippocampal neurons (Lee et al, 2010;Vellano et al, 2011a) Anxiety (Parker et al, 2012) H-Ras at the R1 Ras binding domain (Willard et al, 2009;Vellano et al, 2013) Piriform cortex (Grafstein-Dunn et al, 2001;Evans et al, 2014) NA Ga i1/3 at the GPR (GoLoco) motif (Hollinger et al, 2001;Kimple et al, 2001;Mittal and Linder, 2004) Orbital cortex (Evans et al, 2014) Striatum ( …”