Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In vivo polycystin-1 interactome using heads of Pkd1 knock-in newborn mice

ABSTRACT: We generated a new mouse model with three copies of the HA epitope and eGFP knocked-in frame into the endogenous mouse Pkd1 gene by CRISPR/Cas9. The modified allele is fully functional. Using nanobody-coupled beads and large quantities of tissue (8 heads of P1 newborn mice / experiment / condition), we immunoprecipitated a PC1 interactome that was characterized by mass spectrometry.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Polycystic Kidney Disease

SUBMITTER: David Anderson

LAB HEAD: Gregory George Germino

PROVIDER: PXD035250 | Pride | 2023-08-08

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	CCLINseq.fasta	Fasta
	Chicken.fasta	Fasta
	Mouse071119.fasta	Fasta
	Pierce15.fasta	Fasta
	allSpectra.HCD.ITMS.iso_0.apl	Other

Items per page:

1 - 5 of 1665

Publications

In vivo Polycystin-1 interactome using a novel Pkd1 knock-in mouse model.

Lin Cheng-Chao CC Menezes Luis F LF Qiu Jiahe J Pearson Elisabeth E Zhou Fang F Ishimoto Yu Y Anderson D Eric DE Germino Gregory G GG

PloS one 20230804 8

PKD1 is the most commonly mutated gene causing autosomal dominant polycystic kidney disease (ADPKD). It encodes Polycystin-1 (PC1), a putative membrane protein that undergoes a set of incompletely characterized post-transcriptional cleavage steps and has been reported to localize in multiple subcellular locations, including the primary cilium and mitochondria. However, direct visualization of PC1 and detailed characterization of its binding partners remain challenging. We now report a new mouse ...[more]

PMID: 37540694

Similar Datasets

Identification of biomarkers for PKD1 using urinary exosomes

Project description:Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of ESRD. Affected individuals inherit a defective copy of either the PKD1 or PKD2 gene, encoding the proteins polycystin?1 (PC1) or polycystin?2 (PC2) respectively. PC1 and PC2 are secreted on urinary exosome?like vesicles (ELVs) (100nm diameter vesicles), where PC1 is present in a cleaved form and may be complexed with PC2. Label free quantitative proteomic studies of urine ELVs in an initial discovery cohort (13 PKD1 and 18 Normals), revealed that of 2008 ELV proteins, nine (0.32%) showed a statistically significant difference between PKD1 and normals at a p<0.025. PC1 was reduced to 54% of the normal level (p<0.02) and PC2 reduced to 53% (p<0.001). TMEM2, a protein with homology to fibrocystin, the product of the polycystic hepatic and kidney disease (PKHD1) gene, is increased 2.1 fold (p<0.025). The PC1/TMEM2 ratio correlated inversely with height adjusted total kidney volume (HtTKV) in the discovery cohort and the ratio of PC1/TMEM2 or PC2/TMEM2 could be used to distinguish PKD1 from normals in a confirmation cohort. In summary, this study suggests that a test based on the urine exosomal PC1/TMEM2 or PC2/TMEM2 ratio may have utility in the diagnosis and perhaps monitoring of PKD1.

2014-12-02 | PXD001075 | Pride

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion

Project description:Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.

2023-02-17 | PXD040210 | Pride

Bulk RNA-Seq of Drosophila melanogaster heads after sl knockdown in glia versus control

Project description:In a genetic screen we identified that glial knockdown of small wing (sl) impacts engulfment of dying neurons. To understand the roles of glial sl further, we performed bulk transcriptomics. Here we extracted RNA from pooled Drosophila heads after sl knockdown using the repo-GAL4 driver and compared gene expression to an RNAi control.

2024-06-01 | E-MTAB-14080 | biostudies-arrayexpress

Identification of biomarkers for PKD1 using urinary exosomes

2016-03-01 | MSV000079547 | MassIVE

RNA-seq of depdc5-/-, tsc2-/-, depdc5-/- x tsc2-/- and wildtype zebrafish larvae

Project description:Transcriptome analysis of the heads of 5 dpf epdc5-/-, tsc2-/-, depdc5-/- x tsc2-/- and wildtype zebrafish larvae to provide insights into the neuropathological processes underlying the observed epileptic phenotype in sv2a-/- zebrafish larvae.

2022-09-12 | E-MTAB-11776 | biostudies-arrayexpress

The distinct N-terminomes of Bothrops jararaca newborn and adult venoms.

Project description:In this study we applied the Terminal Amine Isotopic Labeling of Substrates (TAILS) technology to characterize the natural N-terminome of newborn and adult Bothrops jararaca venoms.

2021-05-15 | PXD022696 | Pride

Project description:Background: Autosomal dominant polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby the loss/loss-of-function of polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been implicated in cystogenesis, while we have shown that the RhoA/cytoskeleton/myocardin-related transcription factor (MRTF) pathway is a key inducer of epithelium-induced fibrogenesis. Therefore, we hypothesized that MRTF 1) is activated by PC1/2 loss, and 2) plays a critical role in fibrogenic repogramming of the epithelium and the subsequent induction of fibrosis. Methods: PC1/2 loss was achieved by gene silencing in tubular cells (in vitro) and in PKD1 (RC/RC) and PKD2 (ws25/-) mice (in vivo). RhoA activation was measured by pull-down assays and immunofluorescence. MRTF localization (nuclear/cytosolic ratio, intensity) was quantified in large cell populations and in renal tissue using automated image analysis. PC1/PC2 loss-promoted, MRTF-dependent gene expression was followed by qPCR, RNAseq and RNAscope. MRTF-dependent paracrine effects were assessed by a bioassay. Results: Loss of PC1 or PC2 activated RhoA in vitro and in vivo, resulting in cytoskeletal remodelling and robust nuclear MRTF translocation, accompanied by increased MRTF expression. Nuclear translocation occurred predominantly in dilated tubules, while overexpression in the cyst-lining epithelium. A large cohort of PC1/PC2 downregulation-induced genes was MRTF-dependent, including cytoskeletal, integrin-related, and matricellular/fibrogenic proteins. Epithelial MRTF was necessary for paracrine priming of fibroblast-myofibroblast transition. Conclusion: The Rho/MRTF pathway is a critical novel mediator of PC1/2 loss-induced acquisition of the profibrotic epithelial phenotype and the ensuing fibrosis.

2024-05-01 | GSE252716 | GEO

HSF4 microarray gene expression analysis in the newborn mouse lens.

Project description:Differential expression of HSF4 in null newborn mouse and wildtype lenses was examined to identify putative downstream targets of HSF4. To examine roles of Brg1 in mouse lens development, a dnBrg1 transgenic construct was expressed using the lens-specific aA-crystallin promoter in postmitotic lens fiber cells. Morphological studies revealed abnormal lens fiber cell differentiation in transgenic lenses resulting in cataract. Electron microscopic studies showed abnormal lens suture formation and incomplete karyolysis (denucleation) of lens fiber cells. To identify genes regulated by Brg1, RNA expression profiling was performed in E15.5 embryonic wild type and dnBrg1 transgenic lenses. In addition, comparisons between differentially expressed genes in dnBrg1 transgenic, Pax6 heterozygous, and Hsf4 homozygous lenses identified multiple genes co-regulated by Brg1, Hsf4 and Pax6. Among them DNase IIb, a key enzyme required for lens fiber cell denucleation, was found downregulated in each of the Pax6, Brg1 and Hsf4 model systems. Lens-specific deletion of Brg1 using conditional gene targeting demonstrated that Brg1 was required for lens fiber cell differentiation and indirectly for retinal development but was not essential for lens lineage formation. Keywords: Differential mRNA Expression Three biological replicate experiments were performed with HSF null and wildtype lenses.

2010-12-01 | E-GEOD-22362 | biostudies-arrayexpress

DNA methylation in newborn cordblood

Project description:There is extensive variation in DNA methylation between individuals and ethnic groups. These differences can arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we have assayed genome-wide DNA methylation in neonatal cord blood from African American, European American, and other ancestral groups. This is part of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our overarching goal is to determine the different environmental and maternal factors that can modify DNA methylation in newborns. This is a cross-sectional study of a total of 216 racially diverse participants of CANDLE. Cordblood was collected at birth. DNA methylation was measured using the Illumina HumanMethylation27 BeadChip. Based on maternal self-report, the samples are 112 African Americans, 91 European Americans and 13 other racial or mixed race group.

2015-01-14 | E-GEOD-64940 | biostudies-arrayexpress

The E3 Ligase CUL3 physically interacts with TANGO10 protein in vivo

Project description:List of protein scores for putative TANGO10 interactors from mass spectrometry analysis of FLAG-tagged TANGO10 using either elav-GAL4 or tim-GAL4 at both ZT10 and ZT 22, as determined using Proteome Discoverer software (ThermoFisher). Fly heads from GAL4 heterozygotes were used as controls. The hits from FLAG-tagged twenty-four (TYF) proteomics were also excluded from the list to increase TANGO10-specificity. Proteins listed are those present in at least one elav-GAL4 sample and at least one tim-GAL4 sample but no negative controls.

2021-11-02 | PXD029326 | Pride

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