Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons

ABSTRACT: Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE126841 | GEO | 2019/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through b-adrenoceptors

Project description:Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important to maintain cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for alfa1-adrenoceptor (alfa1AR)-stimulated cation entry and their upregulation is reportedly associated with pathological cardiac remodeling, but whether TRPC channels participate in physiological pump functions remains unclear. Here, we demonstrate that TRPC6-specific Zn2+ influx potentiates alfa-adrenoceptor (alfaAR)-stimulated positive inotropy in rodent cardiomyocytes. Deletion of the trpc6 gene impairs sympathetic nerve-activated positive inotropy, but not chronotropy in mice. TRPC6-mediated Zn2+ influx boosts alfa1AR-stimulatedalfaAR/Gs-dependent signaling in rat cardiomyocytes by inhibiting alfa-arrestin-mediated alfaAR internalization. Replacing two TRPC6-specific amino acids in the pore region with those of TRPC3 diminishes the alfa1AR-stimulated Zn2+ influx and positive inotropic response. Pharmacological enhancement of TRPC6-mediated Zn2+ influx prevents the progression of heart failure in dilated cardiomyopathy mice. Our data provide evidence that TRPC6-mediated Zn2+ influx with α1AR stimulation enhances baroreflex-induced positive inotropy, which may be a new therapeutic strategy for chronic heart failure.

2022-09-14 | GSE189494 | GEO

Transcriptional response of Streptococcus pneumoniae to Zn2+-limitation and the repressor/activator function of AdcR

Project description:Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. This SuperSeries is composed of the SubSeries listed below.

2011-05-13 | GSE29236 | GEO

Transcriptional response of Streptococcus pneumoniae to Zn2+-limitation and the repressor/activator function of AdcR

Project description:Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. Two condition design comparison of Wild-type strain including a dye swap Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE29234: adcR mutant vs wild type D39 GSE29235: Low Zn vs high Zn in CDM

2011-05-13 | E-GEOD-29236 | biostudies-arrayexpress

Structural determinants of specificity and antagonistic Ca2+ and Zn2+ regulation of peptidase activity in human KLK8/neuropsin

Project description:Human KLK8/neuropsin, a kallikrein-related serine peptidase, is mostly expressed in skin and hippocampus, where it regulates memory formation by synaptic remodeling. Recombinantly expressed KLK8 revealed a good accordance two substrate profiling methods: positional scanning with fluorogenic tetrapeptides and a novel version of the proteomic PICS approach. Besides a strong preference for Arg in the P1 position, the enzyme favors Thr in P4, basic P3 residues, aliphatic P2, small P1′ and aliphatic P2′ residues. Enzyme kinetic studies with synthesized substrates showed stimulatory and inhibitory effects of Ca2+ and Zn2+, respectively, which are important for physiological functions. Two crystal structures of KLK8 with the active site inhibitor leupeptin explain the subsite specificity and display Ca2+ bound to the 75-loop, which is unique among the KLKs. The mutants D70K and H99A confirmed the antagonistic role of the cation binding sites, for which a comparison with the murine apo-KLK8 structure clarified further mechanistic details. Molecular docking and dynamics calculations provided insights in substrate binding and the dual regulation by Ca2+ and Zn2+, involving an allosteric surface loop network.

2018-10-17 | PXD006884 | Pride

Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons

Project description:Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons

| PRJNA523443 | ENA

The regulation of the AdcR regulon in Streptococcus pneumoniae depends both on Zn2+- and Ni2+- availability

Project description:By using the transcriptomic approach, we have elucidated the effect of Ni2+ on the global gene expression of S. pneumoniae D39 by identifying several differentially expressed genes/operons in the presence of a high extracellular concentration of Ni2+. The genes belonging to the AdcR regulon (adcRCBA, adcAII-phtD, phtA, phtB and phtE) and the PsaR regulon (pcpA, prtA and psaBCA) were highly upregulated in the presence of Ni2+. We have further studied the role of Ni2+ in the regulation of the AdcR regulon by using ICP-MS analysis, electrophoretic mobility shift assays and transcriptional lacZ-reporter studies, and demonstrate that Ni2+ is directly involved in the derepression of the AdcR regulon via the Zn2+-dependent repressor AdcR, and has an opposite effect on the expression of the AdcR regulon as compared to Zn2+. This SuperSeries is composed of the SubSeries listed below.

2015-11-20 | GSE73852 | GEO

Proteus terrae subsp. cibarius strain:ZN2

Project description:Proteus terrae subsp. cibarius strain:ZN2 Genome sequencing

| PRJNA599040 | ENA

Human immunodeficiency reveals the Zn2+-dependence of B cell development

Project description:Despite the known importance of zinc for human immunity, molecular insights into its roles remain limited. Here we report a novel autosomal recessive disease characterised by early-onset infections, absent B cells and agammaglobulinaemia in five unrelated families. The immunodeficiency results from a series of hypomorphic and null alleles of SLC39A7, which encodes the endoplasmic-reticulum-to-cytoplasm zinc transporter, ZIP7. Using CRISPR-Cas9 editing and homologous recombination we have modelled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic lethality, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited increased phosphatase activity and decreased phosphorylation of signalling molecules that lie downstream of the pre-B and B cell receptors. Our findings highlight a specific role for Zn2+ in modulating B cell receptor signal strength and positive selection, and suggest how Zn2+ could modulate outcome in a variety of signalling contexts.

2018-11-19 | GSE108178 | GEO

Remodeling of Zn2+ Homeostasis Upon Differentiation of Mammary Epithelial Cells

Project description:Remodeling of Zn2+ Homeostasis Upon Differentiation of Mammary Epithelial Cells

| PRJNA602910 | ENA

Human immunodeficiency reveals the Zn2+-dependence of B cell development

Project description:Human immunodeficiency reveals the Zn2+-dependence of B cell development

| PRJNA422757 | ENA