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

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.

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive behavior

“…To identify the CeL/CeC, we performed immunohistochemistry against PKC-δ (30) or the regulator of G protein signaling 14 (RGS14) (66–68) as the restricted pattern of RGS14 immunoreactivity to the CeL/CeC was observed in the present study (Fig. 3D, H).…”

Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease

“…The RGS14 gene encodes a multi-functional nucleocytoplasmic shuttling signaling protein involved in modulating microtubule dynamics and spindle formation ( 46 ). RGS14 acts as a scaffolding protein that integrates the G protein, Ras/extracellular signal-regulated kinase (ERK), and calcium/calmodulin signaling pathways essential for spine plasticity and cell signaling ( 52 ); RGS14 may also reduce hepatic ischemia–reperfusion injury mainly through its interaction with TAK1 and the JNK/p38 signaling axis ( 53 ). IFT140 is a key component of IFT complex A, which is responsible for retrograde transportation in cilia.…”

Min pig skeletal muscle response to cold stress

“…Three genes were downregulated in both groups: RGS14 , MTX3 , and TMEM139 . RGS14 can regulate post synaptic plasticity in neurons [ 41 ] and TMEM139 is involved in substance transport [ 42 ].…”