Regulator of G protein signalling 14 (RGS14) protein expression profile in the adult mouse brain.

Regulator of G protein signalling 14 (RGS14) is a multifunctional signalling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with monkey brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra and amygdala.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits.

Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport.

Parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) control serum phosphate levels by downregulating the renal Na-phosphate transporter NPT2A, thereby decreasing phosphate absorption and augmenting urinary excretion. This mechanism requires NHERF1, a PDZ scaffold protein, and is governed by the regulator of G protein signaling-14 (RGS14), which harbors a carboxy-terminal PDZ ligand that binds NHERF1. RGS14 is part of a triad of structurally related RGS proteins that includes RGS12 and RGS10.

Regulator of G Protein Signaling 14 protein expression profile in the adult mouse brain.

Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with adult rhesus macaque brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra, and amygdala in the adult rhesus monkey brain.

The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.

Mechanisms of mGluR-dependent plasticity in hippocampal area CA2.

Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long-term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several known and potential regulators of metabotropic glutamate receptor (mGluR)-dependent signaling including Striatal-Enriched Tyrosine Phosphatase (STEP) and several Regulator of G-protein Signaling (RGS) proteins, yet the functions of these proteins in regulating mGluR-dependent synaptic plasticity in CA2 are completely unknown.

RGS14 is neuroprotective against seizure-induced mitochondrial oxidative stress and pathology in hippocampus.

RGS14 is a complex multifunctional scaffolding protein that is highly enriched within pyramidal cells (PCs) of hippocampal area CA2. There, RGS14 suppresses glutamate-induced calcium influx and related G protein and ERK signaling in dendritic spines to restrain postsynaptic signaling and plasticity. Previous findings show that, unlike PCs of hippocampal areas CA1 and CA3, CA2 PCs are resistant to a number of neurological insults, including degeneration caused by temporal lobe epilepsy (TLE).

RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.

RGS14 is a multifunctional scaffolding protein that is highly expressed within postsynaptic spines of pyramidal neurons in hippocampal area CA2. Known roles of RGS14 in CA2 include regulating G protein, H-Ras/ERK, and calcium signaling pathways to serve as a natural suppressor of synaptic plasticity and postsynaptic signaling. RGS14 also shows marked postsynaptic expression in major structures of the limbic system and basal ganglia, including the amygdala and both the ventral and dorsal subdivisions of the striatum.

Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis.

Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling by acting as negative regulators of G proteins. Genetic variants in RGS proteins are associated with many diseases, including cancers, although the impact of these mutations on protein function is uncertain. Here we analyze the RGS domains of 15 RGS protein family members using a novel bioinformatic tool that measures the missense tolerance ratio (MTR) using a three-dimensional (3D) structure (3DMTR).

RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.

Phosphate homeostasis, mediated by dietary intake, renal absorption, and bone deposition, is incompletely understood because of the uncharacterized roles of numerous implicated protein factors. Here, we identified a novel role for one such element, regulator of G protein signaling 14 (RGS14), suggested by genome-wide association studies to associate with dysregulated Pi levels. We show that human RGS14 possesses a carboxy-terminal PDZ ligand required for sodium phosphate cotransporter 2a (NPT2A) and sodium hydrogen exchanger regulatory factor-1 (NHERF1)-mediated renal Pi transport.

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.

RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.

The regulator of G-protein signaling 14 (RGS14) is a multifunctional signaling protein that regulates post synaptic plasticity in neurons. RGS14 is expressed in the brain regions essential for learning, memory, emotion, and stimulus-induced behaviors, including the basal ganglia, limbic system, and cortex. Behaviorally, RGS14 regulates spatial and object memory, female-specific responses to cued fear conditioning, and environmental- and psychostimulant-induced locomotion.

RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures.

Rationale: In rodents, exposure to novel environments or psychostimulants promotes locomotion. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addiction. RGS14 is a plasticity-restricting protein with unique functional domains that enable it to suppress ERK-dependent signaling as well as regulate G protein activity.

Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons.

The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and dendritic spine localization are essential for RGS14 functions.

Specific Proteomes of Hippocampal Regions CA2 and CA1 Reveal Proteins Linked to the Unique Physiology of Area CA2.

The hippocampus is well established as an essential brain center for learning and memory. Within the hippocampus, recent studies show that area CA2 is important for social memory and is an anomaly compared to its better-understood neighboring region, CA1. Unlike CA1, CA2 displays a lack of typical synaptic plasticity, enhanced calcium buffering and extrusion, and resilience to cell death following injury.

14-3-3γ binds regulator of G protein signaling 14 (RGS14) at distinct sites to inhibit the RGS14:Gα-AlF signaling complex and RGS14 nuclear localization.

Regulator of G protein signaling 14 (RGS14) is a multifunctional brain scaffolding protein that integrates G protein and Ras/ERK signaling pathways. It is also a nucleocytoplasmic shuttling protein. RGS14 binds active Gα via its RGS domain, Raf and active H-Ras-GTP via its R1 Ras-binding domain (RBD), and inactive Gα via its G protein regulatory (GPR) domain.

RGS14 Restricts Plasticity in Hippocampal CA2 by Limiting Postsynaptic Calcium Signaling.

Pyramidal neurons in hippocampal area CA2 are distinct from neighboring CA1 in that they resist synaptic long-term potentiation (LTP) at CA3 Schaffer collateral synapses. Regulator of G protein signaling 14 (RGS14) is a complex scaffolding protein enriched in CA2 dendritic spines that naturally blocks CA2 synaptic plasticity and hippocampus-dependent learning, but the cellular mechanisms by which RGS14 gates LTP are largely unexplored. A previous study has attributed the lack of plasticity to higher rates of calcium (Ca) buffering and extrusion in CA2 spines.

Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease.

Regulators of G protein signaling (RGS) proteins modulate the physiologic actions of many neurotransmitters, hormones, and other signaling molecules. Human RGS proteins comprise a family of 20 canonical proteins that bind directly to G protein-coupled receptors/G protein complexes to limit the lifetime of their signaling events, which regulate all aspects of cell and organ physiology. Genetic variations account for diverse human traits and individual predispositions to disease.

Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (Ca/CaM) and CaM Kinase II (CaMKII) Binding Partner.

Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates G protein and MAPK signaling pathways. In the adult mouse brain, RGS14 is predominantly expressed in hippocampal CA2 neurons where it naturally inhibits synaptic plasticity and hippocampus-dependent learning and memory. However, the signaling proteins that RGS14 natively engages to regulate plasticity are unknown.

Endogenous RGS14 is a cytoplasmic-nuclear shuttling protein that localizes to juxtanuclear membranes and chromatin-rich regions of the nucleus.

Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory. However, to date, little is known about the subcellular distribution and roles of endogenous RGS14 in a neuronal cell line. Most of what is known about RGS14 cellular behavior is based on studies of tagged, recombinant RGS14 ectopically overexpressed in unnatural host cells.

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.

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.

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

The regulator of G protein signaling (RGS) family of proteins serves critical roles in G protein-coupled receptor (GPCR) and heterotrimeric G protein signal transduction. RGS proteins are best understood as negative regulators of GPCR/G protein signaling. They achieve this by acting as GTPase activating proteins (GAPs) for Gα subunits and accelerating the turnoff of G protein signaling.