Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual proteomics of infected macrophages identifies potential novel players involved in Francisella cell to cell dissemination

ABSTRACT: dual proteomics, merocytophagy, intracellular parasitism, Francisella tularensis

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Francisella Tularensis Subsp. Novicida (strain U112) Mus Musculus (mouse)

TISSUE(S): Cell Suspension Culture

SUBMITTER: Cerina Chhuon

LAB HEAD: Guerrera Ida Chiara

PROVIDER: PXD035145 | Pride | 2024-03-29

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	211130_AlCH_HeRY_nE_LFQ_n1-5_I1_2627.d.zip	Other
	211130_AlCH_HeRY_nE_LFQ_n1-5_I2_2628.d.zip	Other
	211130_AlCH_HeRY_nE_LFQ_n1-5_I3_2629.d.zip	Other
	211130_AlCH_HeRY_nE_LFQ_n1-5_I4_2630.d.zip	Other
	211130_AlCH_HeRY_nE_LFQ_n1-5_I5_2631.d.zip	Other

Items per page:

1 - 5 of 31

Similar Datasets

mTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions

Project description:Ferroptosis constitutes a promising therapeutic strategy against cancer by efficiently targeting the highly tumorigenic and treatment-resistant cancer stem cells (CSCs). We previously showed that the lysosomal iron-targeting drug Salinomycin (Sal) was able to eliminate CSCs by triggering ferroptosis. Here, in a well-established breast CSCs model (human mammary epithelial HMLER CD24low/CD44high), we identified that pharmacological inhibition of mechanistic target of rapamycin (mTOR), suppresses Sal-induced ferroptosis. Mechanistically, mTOR inhibition modulates iron cellular flux and prevents the iron and ROS bursts induced by Sal. Besides, integration of multi-omics data identified mitochondria as a key target of Sal action. We demonstrated that mTOR inhibition prevents Sal-induced mitochondrial functional and structural alteration, and that Sal-induced metabolic plasticity is mainly dependent on the mTOR pathway. Overall, our findings provide experimental evidences on the detailed mechanisms of mTOR as a crucial effector of Sal-induced ferroptosis, and gives proof-of-concept that careful evaluation of such combination therapy (here mTOR and ferroptosis co-targeting) is required for effective treatment.

2023-12-20 | PXD041545 | Pride

LC-MS/MS proteomics analysis of neuronal cells and secretomes with timsTOF Pro

Project description:The neuropeptide VGF was recently proposed as a neurodegeneration biomarker. The Parkinson's disease-related protein leucine-rich repeat kinase 2 (LRRK2) regulates endolysosomal dynamics, a process that involves SNARE-mediated membrane fusion and could regulate secretion. Here we investigate potential biochemical and functional links between LRRK2 and v-SNAREs. We find that LRRK2 directly interacts with the v-SNAREs VAMP4 and VAMP7. Secretomics reveals VGF secretory defects in VAMP4 and VAMP7 knockout (KO) neuronal cells. In contrast, VAMP2 KO "regulated secretion-null" and ATG5 KO "autophagy-null" cells release more VGF. VGF is partially associated with extracellular vesicles and LAMP1+ endolysosomes. LRRK2 expression increases VGF perinuclear localization and impairs its secretion. Retention using selective hooks (RUSH) assays show that a pool of VGF traffics through VAMP4+ and VAMP7+ compartments, and LRRK2 expression delays its transport to the cell periphery. Overexpression of LRRK2 or VAMP7-longin domain impairs VGF peripheral localization in primary cultured neurons. Altogether, our results suggest that LRRK2 might regulate VGF secretion via interaction with VAMP4 and VAMP7.

2023-01-31 | PXD028321 | Pride

Unravelling the function of GEXP15, a regulator of Protein Phosphatase type 1, in Plasmodium falciparum

Project description:The Protein Phosphatase type 1 catalytic subunit (PP1c) works in combination with an array of regulatory proteins to specifically dephosphorylate a diverse range of substrates in the cell. In the human malaria parasite, Plasmodium falciparum, this phosphatase and its regulators are poorly characterized. In this study, we employed a multi-faceted approach to investigate the structural and functional characteristics of a conserved Plasmodium specific regulator known as Gametocyte EXported Protein 15, GEXP15. In-silico study highlights three significant regions of interest, an PP1-interacting RVxF motif located in its N-terminal region, a conserved domain whose function is unknown, and a GYF-like domain that may mediate specific protein-protein interactions. In vitro interaction studies shows that GEXP15 has a direct interaction with PP1 via the RVxF binding motif, enhancing its phosphatase activity. Using transgenic GEXP15-tagged line, confocal microscopy reveals that GEXP15 is highly expressed in late asexual stages and is localized in the parasite nucleus. Immunoprecipitation assays followed by mass spectrometry analyses shows its interaction with ribosomal and RNA binding proteins. Furthermore, pulldown analyses of His-tagged recombinant functional domains of GEXP15 confirm its binding to the ribosomal complex via the GYF domain. Our study provides the first insight into the PfGEXP15-PP1-ribosome interaction, crucial for protein translation, and supports PfGEXP15 as a potential target for malaria drug development.

2023-10-24 | PXD042114 | Pride

Mice retina proteomic in the study of gaptch11 in Leber Congenial Amaurosis

Project description:Leber Congenial Amaurosis (LCA) is the most severe early-onset type of blindness that affects children. Several genes have been discovered to be involved in the disease, Gpatch11 being one of them, which needs to be studied deeply. We identified an homozygous variant in the splicing site of exon4 responsible for the deletion in frame of this exon which encoded a part of the gpatch domain. The aim of the project is the understanding of GPATCH11 protein role and more precisely the role of the gpatch domain in the retina. We are interested in dissecting the interaction between wildtype/mutant protein encoded by the gene in respect of an unknown protein (some publication rapported possible interaction with Helicases). This aim could be achieved thanks to the immunoprecipitation of the protein extracted from patients and control fibroblasts and the consequent analysis through mass spectrometry.

2024-09-27 | PXD051363 | Pride

Mice retina proteomic in the study of gaptch11 in Leber Congenial Amaurosis

2024-09-27 | PXD041849 | Pride

Primary Cilia-Autophagy Axis in Hippocampal Neurons Is Essential to Maintain Cognitive Fitness

Project description:A central hallmark of brain aging is the alteration of neuronal functions in the hippocampus, leading to a progressive decline in learning and memory. Multiple reports have shown the importance of blood-borne factors in inter-tissue communication for the maintenance of cognitive fitness and proper regulation of neuronal homeostasis throughout life. Among these blood-borne factors, we identified Osteocalcin (OCN), a bone-derived hormone. OCN induces autophagy machinery in hippocampal neurons which is essential for activity-dependent synaptic plasticity. However, the way in which blood-borne factors like OCN communicate with neurons, including their regulatory mechanisms, remains largely elusive. Here, we show the importance of a core primary cilium (PC)-proteins/autophagy machinery axis in hippocampal neurons that mediate the effects of the pro-youthful blood factor OCN on neuronal homeostasis and cognitive fitness. We found that OCN’s receptor, GPR158, is present at the PC of hippocampal neurons and mediates the regulation of autophagy machinery by OCN. During aging, PC-core proteins are reduced in hippocampal neurons and associated with neuronal PC morphological abnormalities. Restoring their levels is sufficient to improve neuronal autophagy and cognitive impairments in aged mice. Mechanistically, we found that OCN promotes neuronal autophagy in the hippocampus by the induction of PC-dependent cAMP response element-binding protein (CREB) signaling pathway. Altogether, this study proposes a novel paradigm for blood factor-neuron communication dependent on a neuronal PC/autophagy axis by identifying a novel regulatory pathway fostering cognitive fitness and providing the foundation for autophagy-based therapeutic strategies to treat age-related cognitive dysfunction.

2024-11-07 | PXD056975 | Pride

Role of EVs in inflammation propagation and oxidative stress during vascular calcification

Project description:Role of EVs in inflammation propagation and oxidative stress during vascular calcification

2022-05-19 | PXD029441 | Pride

Oenothera effect on senescent NDHF

Project description:Accumulation of senescent dermal fibroblasts drives skin aging, impairing the integrity of the extracellular matrix (ECM) and the function of neighbouring cells. One of strategies to manipulate cell senescence include the reactivation of proliferation. Here, a data independent mass spectrometry based proteomic approach has been used to evaluate the effect of an hydrophilic Oenothera biennis cell culture extract (ObHEx) on senescent human dermal fibroblasts. It has been shown that the extract was able to affect the levels of 18 proteins which cluster together and point to mitosis pathways. Indeed the treatment with ObHEx increase the expression of CDK1, replicative helicase complex (MCM2, MCM3, MCM4, MCM5, MCM6, MCM7), condensin I complex (NCAPD2, NCAPH, NCAPG, SMC4, SMC2) and other proteins related to kinetochore (KNTC1, NUF2, TRIP13). This strongly suggests that ObHEx could restore the proliferation of senescent fibroblasts.

2023-03-10 | PXD034222 | Pride

LC-MS/MS interactomics analysis of Praf2 with timsTOF Pro

Project description:LC-MS/MS interactomics analysis of Praf2 using TurboID with timsTOF Pro.

2023-12-20 | PXD029019 | Pride