Regulation of T cell activation, anxiety, and male aggression by RGS2

Oliveira-dos-Santos, Antonio J.; Matsumoto, Goichi; Snow, Bryan E.; Bai, Donglin; Houston, Frank P.; Whishaw, Ian Q.; Mariathasan, Sanjeev; Sasaki, Takehiko; Wakeham, Andrew; Ohashi, Pamela S.; Roder, John; Barnes, Carol A.; Siderovski, David P.; Penninger, Josef

doi:10.1073/pnas.220414397

Cited by 260 publications

(210 citation statements)

References 31 publications

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“…Similarly, an increase only in the present associative learning group A was seen for the membrane interacting protein of RGS16, involved in lipid metabolism and G-protein signaling (Zheng et al 2000). While there is some indication for an involvement of another regulator of G-protein signaling (RGS2) in synaptic plasticity and emotional behavior (Ingi et al 1998;Oliveira-Dos-Santos et al 2000), our finding is the first evidence of a role for RGS16 in these processes. On the other hand, a great body of…”

Section: Expression Of Signal Transduction and Structural Reorganizatmentioning

confidence: 44%

Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

Stork

Stork²,

Pape³

et al. 2001

Learn. Mem.

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In this study we describe changes of gene expression that occur in the basolateral complex of the mouse amygdala (BLA) during the formation of fear memory. Through the combination of a behavioral training scheme with polymerase chain reaction-based expression analysis (subtractive hybridization and virtual Northern analysis) we were able to identify various gene products that are increased in expression after Pavlovian fear conditioning and are of potential significance for neural plasticity and information storage in the amygdala. In particular, a key enzyme of monoamine metabolism, aldehyde reductase, and the protein sorting and ubiquitination factor Praja1, showed pronounced and learning-specific induction six hours after fear conditioning training. Aldehyde reductase and Praja1, including a novel alternatively spliced isoform termed Praja1a, were induced in the BLA depending on the emotional stimulus presented and showed different expression levels in response to associative conditioning, training stress, and experience of conditioned fear. Stress and fear were further found to induce various signal transduction factors (transthyretin, phosphodiesterase1, protein kinase inhibitor-␣) and structural reorganization factors (e.g., E2-ubiquitin conjugating enzyme, neuroligin1, actin, UDP-galactose transporter) during training. Our results show that the formation of Pavlovian fear memory is associated with changes of gene expression in the BLA, which may contribute to neural plasticity and the processing of information about both conditioned and unconditioned fear stimuli.[The Praja1a sequence has been deposited in GenBank data base under accession no. AF335250.]

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Section: Expression Of Signal Transduction and Structural Reorganizatmentioning

confidence: 44%

Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

Stork

Stork²,

Pape³

et al. 2001

Learn. Mem.

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“…Rgs2 encodes regulator of G protein signaling 2, which belongs to a class of proteins that negatively regulate heterotrimeric G proteins by increasing their GTPase activity. RGS2 specifically inhibits G␣ qmediated signaling, and Rgs2 Ϫ/Ϫ mice have impaired anti-viral immunity as a consequence of T cell hyporesponsiveness (35). Whereas the identity of the G protein-coupled receptor(s) (GPCRs) modulated by RGS2 upon Lm infection is unknown, we note that some chemokine receptors are G␣ q -coupled (36).…”

Section: Irg Induction Is Recapitulated By Cytoplasmic Localization Omentioning

confidence: 85%

A specific gene expression program triggered by Gram-positive bacteria in the cytosol

McCaffrey

Fawcett

O’Riordan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

167

168

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Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic vacuole surface. However, mechanisms underlying recognition of pathogens in other cellular compartments remain unclear, and responses elicited by cytosolic challenge are poorly characterized. We therefore used mouse cDNA microarrays to investigate gene expression triggered by infection of bone marrow-derived macrophages with cytosol-and vacuole-localized Listeria monocytogenes (Lm), a model cytosolic pathogen. The resulting gene expression program included two basic categories of induced genes: an ''early͞persistent'' cluster consistent with NF-B-dependent responses downstream of TLRs, and a subsequent ''late response'' cluster largely composed of IFN-responsive genes (IRGs). The early͞persistent cluster was observed upon infection with WT, heat-killed, or mutant Lm lacking listeriolysin O, the pore-forming hemolysin that promotes escape from phagocytic vacuoles. However, the IRG cluster depended on entry of WT Lm into the cytosol. Infection with listeriolysin O-expressing, cytosolic Bacillus subtilis (Bs) strikingly recapitulated the expression profile associated with WT Lm, including IRG induction. IRG up-regulation was associated with MyD88-independent induction of IFN-␤ transcription and activity. Whereas Staphylococcus aureus (Sa) lipoteichoic acid treatment confirmed that many late-response genes could also be stimulated through TLRs, our study identified a cytosol-specific transcriptional program independent of TLR signaling through MyD88. Further characterization of cytosolic surveillance pathway(s) and their points of convergence with TLR-and IFN-dependent pathways will enhance our understanding of the means by which mammals detect and respond to pathogens.

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“…Although it remains to be seen whether the polymorphisms examined in this study are involved in the RGS2 expression level and/or functional activity, the upregulation of RGS2 and consequent attenuated Gaq-mediated GPCR signaling including the 5-HT2AR in the brain may be one of the factors underlying suicidal behavior. RGS2 knockout has been found to decrease aggression in mice (Oliveira-Dos-Santos et al, 2000). In addition, an analysis of a behavioral quantitative trait locus in mouse showed that RGS2 modulated anxiety (Yalcin et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Among this family, regulator of G-protein signaling 2 (RGS2) has recently been reported to be involved in anxiety and aggressive behavior. RGS2-deficient mice displayed an increased anxiety response and decreased aggression (Oliveira-Dos-Santos et al, 2000). The genetic dissection of a behavioral quantitative trait locus study showed that RGS2 modulated anxiety in mice (Yalcin et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Association of RGS2 Gene Polymorphisms with Suicide and Increased RGS2 Immunoreactivity in the Postmortem Brain of Suicide Victims

Cui

Nishiguchi

Ivleva

et al. 2007

Neuropsychopharmacol

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Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C + 2971G, rs4606) genotypes and alleles of the SNP2 (C-395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global po0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population.

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Regulation of T cell activation, anxiety, and male aggression by RGS2

Cited by 260 publications

References 31 publications

Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

A specific gene expression program triggered by Gram-positive bacteria in the cytosol

Association of RGS2 Gene Polymorphisms with Suicide and Increased RGS2 Immunoreactivity in the Postmortem Brain of Suicide Victims

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