Functional redundancy of the three insulin receptors of cockroaches
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1097959 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene duplication is a fundamental evolutionary process which allows to provide opportunities to acquire new gene functions. In the case of the insulin receptor (InR) gene in cockroaches and close-related insects, two successive duplications determined the occurrence of three InR genes: InR2, InR1 and InR3, the last two forming a sister cluster of InR2. The analysis of the sequences in different species and groups did not led to detect positive selection in the divergence of InR1 and InR3. Using the cockroach Blattella germanica as a model, we have determined that InR2 is the gene with the highest expression levels in all the tissues analyzed, both in adult females and males, as well as in nymphs and embryos. InR3 is second in expression levels while InR1 is expressed at lower levels and only in some tissues. The selective depletion by RNAi of each of the three InRs, analyzed in terms of phenotype and fat body transcriptomes, produced essentially redundant effects, with a magnitude approximately proportional to the level of expression of the respective InR. Therefore, the results indicate that the InR duplicates experienced a subfunctionalization process, by which the three InRs maintained similar functions but contributing to those functions proportionally to their expression levels.
2025-01-28 | GSE263519 | GEO
Project description:We reveal a critical role of tanycyte insulin receptors in gating feeding state-dependent regulation of AgRP neurons and systemic insulin sensitivity, and show that insulin resistance in tanycytes contributes to the pleiotropic manifestations of obesity-associated insulin resistance
2021-12-13 | GSE185074 | GEO
Project description:Insulin receptors in tanycytes gate hypothalamic insulin uptake and regulate AgRP neuronal activity
| PRJNA767609 | ENA
Project description:Despite a high degree of homology, insulin and IGF-1 receptors (IR/IGF1R) mediate distinct cellular and physiological functions. Here, using chimeric and site-mutated receptors, we demonstrate how domain differences between IR and IGF1R contribute the distinct functions of these receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to its higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. We generated mouse brown preadipocytes in which both insulin and IGF-1 receptors (IR and IGF1R) had been genetically inactivated using Cre-lox recombination. These IR and IGF1R DKO cells were then reconstituted with wild-type mouse IR, IGF1R, or one of two chimeric receptors: IR/IGF1R with the IR extracellular domain (ECD) fused to the IGF1R transmembrane and intracellular domains (ICD) and IGF1R/IR with the ECD of IGF1R fused to the ICD domains of IR. Three independent clones for each line were used for the study. For expression analysis, we serum-starved the preadipocytes clones overnight and stimulated cells with 100 nM insulin, IGF-1 or vehicle for 6 h, and subjected the cellular RNA to analysis using Affymetrix Mouse Gene 2.0 ST arrays.
2016-07-01 | E-GEOD-81921 | biostudies-arrayexpress
Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
2022-12-06 | GSE220253 | GEO
Project description:Extensive Functional Redundancy of Mammalian Enhancers
| PRJNA362215 | ENA
Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
2023-11-20 | PXD038950 | Pride
Project description:Mitotic bookmarking redundancy by nuclear receptors mediates robust post-mitotic reactivation of the pluripotency network
| PRJNA909301 | ENA
Project description:Despite a high degree of homology, insulin and IGF-1 receptors (IR/IGF1R) mediate distinct cellular and physiological functions. Here, using chimeric and site-mutated receptors, we demonstrate how domain differences between IR and IGF1R contribute the distinct functions of these receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to its higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation.
2016-07-01 | GSE81921 | GEO
Project description:Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.
2019-04-20 | GSE130098 | GEO