Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Plasmodium Circumsporozoite Protein Promotes the Development of the Liver Stages of the Parasite

ABSTRACT: The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes. Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasite’s advantage. Keywords: treatment and construct

ORGANISM(S): Homo sapiens

PROVIDER: GSE8784 | GEO | 2007/10/30

SECONDARY ACCESSION(S): PRJNA102079

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of human haptocytes infected with plasmodium reveals circumsporozoite protein promotes the development of the liver stages of the Parasite

Project description:The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes. Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasiteâs advantage. Experiment Overall Design: cells were isolated after inducing CSP and stimulating with TNF

2008-06-16 | E-GEOD-8784 | biostudies-arrayexpress

HDXMS comparison of NFkB (p50(39-350)/RelA(19-321) vs NFkB (p50(39-350)/RelA(19-549)

Project description:HDXMS comparison of NFkB (p50(39-350)/RelA(19-321) vs NFkB (p50(39-350)/RelA(19-549)

2022-04-12 | MSV000089247 | MassIVE

Cytosolic calcium and nuclear calcium-regulated transcription networks in response to ABA and JA

Project description:Calcium acts as a universal second messenger to regulate gene expression in both developmental processes and responses to environmental stresses. Previous studies showed that a number of stimuli can induce calcium increases in the cytoplasm and nucleus, independently. However, the gene expression network deciphering [Ca2+]cyt and/or [Ca2+]nuc signaling pathway remain obscure. Using transgenic Arabidopsis containing a fusion protein, comprising rat parvalbumin (PV) with either a nuclear export sequence (PV-NES) or a nuclear localization sequence (NLS-PV), to selectively buffer the cytosolic or nucleosolic calcium, we identified the [Ca2+]cyt- or /and [Ca2+]nuc-regulated ABA- and MeJA-responsible genes with the Arabidopsis Genome Oligo array.

2018-01-25 | GSE109611 | GEO

Testing LPS induced gene expression in murine MEFs with different NFkB knockout

Project description:NFkB is a family of transcriptional factors that are responsible for inflammatory and immune gene expression. RelA, RelB and cRel are the transactivation domain containing family members. P50 encoded by Nfkb1 is the primary dimerization partner. Many NFkB deficient mice are embryonic lethal. In order to identify NFkB dependent genes, MEF were isolated from Rela-/-cRel-/-, Rela-/-cRel-/-Nfkb1-/- and Rela-/-Relb-/-cRel-/- embryos at E12.5. They were treated with 100ng/ml LPS for 1hr and then profiled gene expression by microarray.

2016-06-27 | E-MTAB-4412 | biostudies-arrayexpress

Dual RNA-sequencing of host and pathogen during Plasmodium berghei infection of hepatocytes in vitro

Project description:We report the dual RNA-sequencing of host and pathogen transcriptomes during Plasmodium berghei liver-stage development in vitro. Unlike traditional transcriptomic approaches that analyze RNA reads separately from host and pathogen, a dual-approach maps the mixed reads to each annotated genome within samples of pathogen-infected host cells. This is a powerful method, as host and pathogen transcriptomes can be analyzed simultaneously. We have taken advantage of this dual-RNA sequencing approach in order to gain insight into Plasmodium liver stage development within host hepatocytes. Huh7.5.1 hepatocytes were infected in vitro with P. berghei sporozoites freshly dissected from infected Anopheles stephansi mosquitos, and cells were collected throughout liver-stage development. This included samples collected at time zero (uninfected hepatocytes and sporozoites before infection), time 24 hours post infection (when the sporozoites have transformed into trophozoites), and time 48-50 hours post infection (when the trophozoites have transformed into liver-stage schizonts).

2018-03-06 | GSE78931 | GEO

The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance

Project description:Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches.

2022-12-05 | MTBLS6505 | MetaboLights

Genome-wide maps of NFKB1/p50 binding dynamics

Project description:We report the application of ChIP-Seq for high-throughput profiling of NFKB1/p50 binding dynamics. The binding profiles were performed under three conditions/models. We first examine the p50 binding in HEK293T cells during G1 and S phase. HEK293T cells were synchronized with double thymidine block method. Before and after release to S phase, ChIP was performed, and chromatin immunoprecipitated DNA was converted to libraries for sequencing with HiSeq 4000. We find that these NFKB1/p50 binding peaks in G1 phase dramatically reduced at S phase. Then, we further examine the p50 binding in HEK293T/TopBP1 cells in response to tamoxifen treatment. These cells have stable expression of TopBP1 activation domain fusion with estrogen receptor. After treatment, chromatin immunoprecipitated DNA was converted to libraries for sequencing with HiSeq 4000. We find that these NFKB1/p50 binding peaks in vehicle control sample dramatically reduced after tamoxifen treatment. Final, we compare the genome wide binding behavior of wild type p50 and mutant p50 2KR (K354R and K356R). HEK293T cells was transfected with plasmids expression HA-tagged wild type or mutation p50. Chromatin immunoprecipitated DNA was converted to libraries for sequencing with HiSeq 4000. We find that both wild type and p50 2KR mutant share similar binding profile. However, in general, p50 mutant has less binding affinity to NFKB binding sites. This study provides a preliminary but solid basis to our understanding of NFKB1/p50 binding dynamics.

2020-08-13 | GSE129618 | GEO

Transcription profiling of mouse hepatocytes reinfected with Plasmodium berghei

Project description:We show that an ongoing malaria blood stage infection impairs the establishment of Plasmodium sporozoites in hepatocytes and that secondary infections can only be established after a previous infection has been cleared from circulation. Using control mice, mice infected with sporozoites only, mice infected by iRBCs only or mice reinfected, we show that this impairment is not due to an effect of the acquired host immune response or to a decrease in host cell survival. Instead, an ongoing blood stage infection leads to a significant increase in the expression of hepcidin, a peptide hormone that is secreted by the liver and controls body iron homeostasis. A rapid increase of hepcidin levels during blood stage infection causes sequestration of iron in storage forms within cells of reticuloendothelial system decreasing its availability in hepatocytes, where it is required for Plasmodium sporozoite establishment.

2010-11-01 | E-TABM-839 | biostudies-arrayexpress

Chronic stress alters the E/I balance of pyramidal neurons in the infralimbic and Prelimbic cortices

Project description:The medial prefrontal cortex (mPFC) is a key brain region involved in controlling working memory, executive function, and self-regulatory behaviours, and its malfunction is a hallmark of several neuropsychiatric disorders such as schizophrenia, depression, and post-traumatic stress disorder. One of the main risk factors for the development of mental illness is chronic stress (CS). Despite some evidence pointing to possible excitation-inhibition (E/I) imbalances caused by CS, the precise mechanism by which CS triggers mPFC dysfunction is not fully understood. Here, using neuroproteomics analysis and whole-cell patch-clamp recordings, we investigated the functional changes in E/I ratio and synaptic drive onto pyramidal neurons and parvalbumin interneurons (PV) in the prelimbic (PL) and infralimbic (IL) cortices, following exposure to 21 days of chronic unpredictable stress. We demonstrate that CS impacts PL- versus IL-pyramidal neurons differently, driving a common decrease in E/I ratio without affecting PV interneurons. Our work brings insightful information and corroborates the hypothesis of stress-induced hypofunction of the mPFC.

2024-10-17 | PXD047291 | Pride

Plasmodium berghei PbeIK2KO sporozoites

Project description:Malaria sporozoites, the form transmitted by mosquitoes, are quiescent while in the insect salivary glands. It is only after the sporozoites are deposited in the hostâs skin, migrate to the liver and infect hepatocytes that the parasites continue the life cycle. We show that the sporozoite latency is an active process that requires phosphorylation of the eukaryotic initiation factor-2Î± (eIF2Î±) by a sporozoite-specific kinase. Inactivation of the kinase gene leads to an overall enhancement of protein synthesis including of silenced liver stage proteins, and inhibits transmission of malaria. Specific inhibition of the eIF2Î± phosphatase by salubrinal has the opposite effect. Thus, to prevent premature transformation into liver stages, Plasmodium sporozoites exploit the same mechanism that regulates stress responses in mammalian cells. 4 samples overall, 2 wt and 2 KO (PbeIK2 knockout) samples

2010-05-16 | E-GEOD-16259 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data