An Elongin-Cullin-SOCS-box Complex Regulates Stress-induced Serotonergic Neuromodulation Stress-induced Serotonergic Neuromodulation
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PROVIDER: PRJNA416495 | ENA |
REPOSITORIES: ENA
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Project description:Neuromodulatory cells transduce environmental information into long lasting behavioral responses. However, the mechanisms governing how defined neuronal cell types influence behavioral plasticity are difficult to characterize. Here we adapted the Translating Ribosome Affinity Purification (TRAP) approach in C. elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing ADF serotonergic sensory neurons, and found that it plays a role in mediating long-lasting change in serotonin-dependent feeding behavior induced by heat stress. We demonstrate that ELC-2 and the von Hippel-Lindau protein VHL-1, components of an Elongin-Cullin-SOCS-box (ECS) E3 ubiquitin ligase, modulate this behavior after experiencing stress. Also, heat stress induces a transient redistribution of ELC-2, becoming more nuclearly enriched. Together, our results demonstrate dynamic regulation of an E3 ligase, and a role for an ECS complex in neuromodulation and control of lasting behavioral states.
2017-11-01 | GSE106374 | GEO
Project description: Not available
| S-EPMC6283282 | biostudies-literature
Project description:Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. Methods We generated transgenic mice constitutively expressing SOCS-3 in skeletal muscle to define whether the sole expression of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 expression, several genes had deregulated expression, among them other members of the SOCS family. This could maintain the insulin signal into skeletal muscle. Interestingly, we found that SOCS-3 interacts with calcineurin, which has been implicated in muscle contractility. In SOCS-3 transgenic muscle, this leads to delocalisation of calcineurin to the fibre periphery. Relevant to this finding, SOCS-3 transgenic animals had dilatation of the sarcoplasmic reticulum associated with swollen mitochondria and decreased voluntary activity. Conclusions/interpretation Our results show that constitutive SOCS-3 expression in skeletal muscle is not in itself sufficient to induce the establishment of metabolic disorders such as diabetes. In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity. (Patricia Lebrun et al, Diabetologia, 2009)
2009-12-31 | GSE17063 | GEO
Project description:Mental disorders are caused by genetic and environmental factors. We here show that deficiency of an isoform of dopamine D2 receptor (D2R), D2LR, causes psychosocial stress vulnerability in mouse. This occurs through dysfunction of type 1A serotonin (5-hydroxytryptamine, 5-HT) receptor (5-HT1AR) on serotonergic neurons in the mouse brain. Exposure to forced swim stress significantly increased anxiety- and depressive-like behaviors in D2LR knockout (D2LR-KO) male mice as compared with wild-type mice. Treatment with 8-OH-DPAT, a 5-HT1AR agonist, failed to alleviate the stress-induced behaviors in D2LR-KO mice. In forced swim-stressed D2LR-KO mice, 5-HT release in the medial prefrontal cortex was elevated and the expression of genes related to 5-HT levels was up-regulated by the transcription factor PET1 in the dorsal raphe nucleus. Notably, D2LR formed a heteromer with 5-HT1AR in serotonergic neurons, thereby suppressing 5-HT1AR–activated G-protein–activated inwardly rectifying potassium (GIRK) conductance in D2LR-KO serotonergic neurons. Finally, D2LR overexpression in serotonergic neurons in the dorsal raphe nucleus alleviated stress vulnerability observed in D2LR-KO mice. Taken together, we conclude that disruption of the negative feedback regulation by the D2LR/5-HT1A heteromer causes stress vulnerability.
2019-01-09 | GSE124806 | GEO
Project description:Performed RNA-seq analysis of animals with xbp-1s overexpression (ER stress response transcription factor) in specific neuron types: pan-neuronal, serotonergic neuron, dopaminergic neuron, and both serotonergic and dopaminergic neurons, all compared to a wild-type control. RNA-seq was performed on purified RNA extracted from ~1000 whole worms using a proprietary Genewiz protocol described briefly in the manuscript. 3 biological replicates are provided for each sample.
2021-01-01 | E-MTAB-9771 | biostudies-arrayexpress
Project description:To investigate the liver transcriptomics of WT and liver Cullin 3 KO mice on chow diect (CD) and Westrn diet (WD)
2024-04-05 | GSE230518 | GEO
Project description: Not available
| S-EPMC1472497 | biostudies-literature
Project description:To further understanding the function of cullin 3 during inflammation in macrophages, we have employed mouse bone marrow derived macrophages microarray expression profiling to identify the gens that involve in regulationg inflammatory respones upon LPS challenge. Mouse BMM were stimulated with LPS for 6 hours and RNA was extracted for microarray. Ogt was indentified by comparison between wildtype and Cullin 3 knockout BMM.
2017-01-06 | GSE93166 | GEO
Project description:Human serotonergic neurons are derived using published transdifferentiation protocols. Human Fibroblasts correspond to human fibroblasts (from Line#1, Coriell bought (AG08498)). Samples labeled human neurons or induced neurons (iN) correspond to neurons transdifferentiated from fibroblasts using two transcription factors, as previously described (#1-AG08498 or #2:ERF-1, Erlangen Germany, a line given to us by collaborators) into primarily glutamatergic neruons. Samples labled 5-HT neurons or serotonergic neurons or iSN correspond to serotonergic neurons derived from the stated fibroblast lines, using an additional four transcription factors. For transdifferentiation of iN and iSN, fibroblasts were made to overexpress the stated transcription factors in a doxycycline inducible manner for up to 3 weeks, and then neurons are sorted out and collected directly into Trizol for RNA preparation and sequencing. The non-transdifferentiated fibroblast lines were collected in bulk withtout differentiation into neurons. The line number corresponds to the same fibroblast line either being transdifferentiated into iN or iSN, as labeled - for direct and groupwise comparison.
2016-02-02 | E-MTAB-3680 | biostudies-arrayexpress
Project description:Transcriptional Regulation by Cullin Ubiquitin Ligases
| PRJNA614537 | ENA