RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain
Open Access
- 25 June 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (13), 6823
- https://doi.org/10.3390/ijms22136823
Abstract
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. At the cellular level, RGS14 acts as a scaffolding protein that integrates G protein, Ras/ERK, and calcium/calmodulin signaling pathways essential for spine plasticity and cell signaling, allowing RGS14 to naturally suppress long-term potentiation (LTP) and structural plasticity in hippocampal area CA2 pyramidal cells. Recent proteomics findings indicate that RGS14 also engages the actomyosin system in the brain, perhaps to impact spine morphogenesis. Of note, RGS14 is also a nucleocytoplasmic shuttling protein, where its role in the nucleus remains uncertain. Balanced nuclear import/export and dendritic spine localization are likely essential for RGS14 neuronal functions as a regulator of synaptic plasticity. Supporting this idea, human genetic variants disrupting RGS14 localization also disrupt RGS14’s effects on plasticity. This review will focus on the known and unexplored roles of RGS14 in cell signaling, physiology, disease and behavior.Funding Information
- National Institutes of Health (R01NS037112 (Hepler, PI) and 2R21NS102652 (Heper, PI))
This publication has 195 references indexed in Scilit:
- RGS4 Is Required for Dopaminergic Control of Striatal LTD and Susceptibility to Parkinsonian Motor DeficitsNeuron, 2012
- Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse LineBehavior Genetics, 2012
- The Expanding Social Network of Ionotropic Glutamate Receptors: TARPs and Other Transmembrane Auxiliary SubunitsNeuron, 2011
- Small G Protein Signaling in Neuronal Plasticity and Memory Formation: The Specific Role of Ras Family ProteinsNeuron, 2010
- Myosin IIb Regulates Actin Dynamics during Synaptic Plasticity and Memory FormationNeuron, 2010
- Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal LoopNeuron, 2010
- RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathwaysCellular Signalling, 2010
- AMPA Receptor Incorporation into Synapses during LTP: The Role of Lateral Movement and ExocytosisNeuron, 2009
- The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network StructureCell, 2009
- Calmodulin-Kinases: Modulators of Neuronal Development and PlasticityNeuron, 2008