Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Purification of time-resolved insulin granules reveals proteomic and lipidomic changes during granule aging

ABSTRACT: Endocrine cells employ regulated exocytosis of secretory granules to secrete hormones and neurotransmitters. Secretory granule exocytosis depends on spatio-temporal variables such as proximity to the plasma membrane and age, with newly-generated granules being preferentially released. Despite recent advances, we lack a comprehensive view about the molecular composition of insulin granules and associated changes over their lifetime. Here we report a strategy for the purification of insulin secretory granules of distinct age from insulinoma INS-1 cells. Tagging the granule-resident protein phogrin with a cleavable CLIP tag, we obtain intact fractions of age-distinct granules for proteomic and lipidomic analyses. We find that the lipid composition changes

INSTRUMENT(S): time-of-flight

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Pancreas

DISEASE(S): Diabetes Mellitus

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD050087 | Pride | 2024-04-15

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	output.rar	Other
	raw.rar	Other

Items per page:

1 - 2 of 2

Similar Datasets

Comparative DDA and DIA-PASEF proteomics profiling of cross-kingdom macrophage infection reveals new mechanisms driving pathogen virulence

Project description:Opportunistic infections of the respiratory tract often succeed under a weakened immune response caused by an underlying illness or hospitalization. The human fungal pathogen, Cryptococcus neoformans, and the bacterial pathogen, Klebsiella pneumoniae, are both well-characterized microbes that cause severe infections within immunocompromised individuals. In this study, we simulate a concentration-dependent pulmonary coinfection of a bacterial and fungal pathogen, and profile the proteomic changes by DDA vs. DIA. Dual perspective profiling provides new insights into host defense regulation of infection and pathogenic mechanisms of invasion.

2024-08-13 | PXD054527 | Pride

Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells induce Oxygen-dependent Cell Invasion

Project description:Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors, is often related to increased extracellular vesicle (EV) secretion and favors cell invasion, which is a crucial step for metastasis. Cell invasion is a complex process in which cell morphology is altered due to F-actin cytoskeleton polarization and the establishment of dynamic focal adhesion spots, which coupled with ECM remodeling enables cells to migrate through tissues seeking a new developmental niche. In our in-depth investigation over the invasive properties triggered by TNBC-derived hypoxic small EVs (SEVh) in vitro, we analyzed the morphological, phenotypical and proteomic distinctions promoted by hypoxia and/or SEVh signaling in TNBC cells. SEVh was fully characterized and showed a distinct proteome and abundance profile from its normoxic counterparts. SEVh promotes invasive behaviors exclusively in normoxia, including pro-migratory morphology, invadopodia development, ECM degradation and gelatinase secretion, which indicates the importance of SEVh response on hypoxic settings in tumor progression. In hypoxia, SEVh was responsible for proteolytic and catabolic pathway inducement, interfering with integrin availability and gelatinase expression. Protein profiling of SEVh-treated, normoxic cells indicate a baseline favoring of metabolic processes and cell cycle, modulating cell health away from apoptotic pathways that are enriched in hypoxia. Overall, our results demonstrate the importance of hypoxic signaling via SEV in a tumoral setting for the early establishment of metastasis.

2022-11-01 | PXD035244 | Pride

Deep Visual Proteomics defines single-cell identity and heterogeneity

Project description:Despite the availabilty of imaging-based and mass-spectrometry-based methods for spatial proteomics, a key challenge remains connecting images with single-cell-resolution protein abundance measurements. Here we introduce Deep Visual Proteomics (DVP), which combines artificial-intelligence-driven image analysis of cellular phenotypes with automated single-cell or single-nucleus laser microdissection and ultra-high-sensitivity mass spectrometry. DVP links protein abundance to complex cellular or subcellular phenotypes while preserving spatial context. By individually excising nuclei from cell culture, we classified distinct cell states with proteomic profiles defined by known and uncharacterized proteins. In an archived primary melanoma tissue, DVP identified spatially resolved proteome changes as normal melanocytes transition to fully invasive melanoma, revealing pathways that change in a spatial manner as cancer progresses, such as mRNA splicing dysregulation in metastatic vertical growth that coincides with reduced interferon signaling and antigen presentation. The ability of DVP to retain precise spatial proteomic information in the tissue context has implications for the molecular profiling of clinical samples.

2022-04-27 | PXD023904 | Pride

VCF1 is a p97 cofactor promoting recruitment of p97-UFD1-NPL4 to ubiquitylated substrates

Project description:The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to ubiquitylated client proteins via multiple cofactors, most of which interact with the p97 N-domain. Here, we discovered that FAM104A, a protein of unknown function that we named VCF1, acts as a novel p97 cofactor in human cells. Detailed structure-function studies revealed that VCF1 directly binds p97 via a conserved novel alpha-helical motif that recognizes the p97 N-domain with unusually high affinity exceeding that of other cofactors. We show that VCF1 engages in joint p97 complex formation with the heterodimeric primary p97 cofactor UFD1-NPL4 and promotes p97-UFD1-NPL4-dependent proteasomal degradation of ubiquitylated substrates in cells. Mechanistically, VCF1 stimulates the affinity of the p97-UFD1-NPL4 complex for ubiquitin conjugates indirectly via its binding to p97 but does not itself interact with ubiquitin. Collectively, our findings establish VCF1 as an unconventional p97 cofactor that promotes p97-dependent protein turnover by facilitating p97-UFD1-NPL4 recruitment to ubiquitylated targets.

2024-03-14 | PXD043565 | Pride

Acute stress induces long-term metabolic, functional and structural remodeling of the heart

Project description:Takotsubo syndrome is a stress-induced cardiomyopathy with symptoms comparable to those of acute coronary syndrome but without coronary obstruction. Initially considered spontaneously reversible, the reversibility of takotsubo was challenged by epidemiological studies showing high morbi-mortality in the long term. Here we explore comprehensively cardiac metabolism, structure and function after a single acute stress. We show that a single pharmacological stress is sufficient to recapitulate the clinical signs of ventricular dysfunction of takotsubo and their apparent reversibility. Interestingly, myocardial glucose metabolic remodeling during the acute phase was also present throughout the late recovery phases. Metabolic stunning where high glucose uptake is derived from glycolysis into alternative non-oxidative pathways such as the hexosamine biosynthetic and polyol pathways parallels with irreversible tissue and vascular remodeling. This study evidences that stress-induced diversion of glucose metabolism is the cause of deleterious structural and functional sequelae in takotsubo hearts.

2023-06-28 | PXD032667 | Pride

Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly

Project description:The aim of this project was to identify cellular factors enriched in SARS-CoV-2 virion preparations from infected Calu-3 cells as compared to preparation from mock-infected cells.

2024-01-22 | PXD045406 | Pride

Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly

Project description:The aim of this project was to identify cellular factors enriched with SARS-CoV-2 virions after affinity capture using biotinylated ACE2 receptor as compared to biotin control.

2024-01-22 | PXD045409 | Pride

Impact of fetal growth restriction on neonatal microglia proteome in rat.

Project description:Microglia activation is a key modulator of brain vulnerability in response to intra-uterine growth restriction (IUGR). However, the consequences of IUGR on microglia development and on microglia proteome are still unknown. We used a model of IUGR induced by a gestational low-protein diet (LPD) in rat. Microglia were isolated from control and LPD animals at P1 and P4. The aim of this work was characterize the consequence of IUGR on microglia development and investigate the consequences of IUGR exposure on microglia proteome during the first postnatal days using a bioinformatics approach associated with functional assays.

2021-12-17 | PXD028950 | Pride

Proteomic analysis neutrophils from COVID-19 patients

Project description:To go further insight into the involvement of neutrophils in COVID-19 clinical expression, we performed a proteomic analysis of this blood cell type in COVID-19 patients and two non-infected SARS-CoV-2 control groups composed of healthy subjects and ARDS patients hospitalized in intensive care unit (ICU) respectively. All patients were from Guadeloupe and represent a homogeneous population. We have performed a quantitative proteomic study of neutrophiles from French hot spot COVID region, Guadeloupe, confirming the activation of type I IFN pathway and in some target of IFN as TAP proteins, specifically in COVID patients, but not in hospitalized ARDS non-COVID patients and described modification of the NET proteome potentially associated with ARDS.

2022-07-27 | PXD033293 | Pride

The Centriolar Satellite Component CEP131 timely regulates mitochondrial Apoptosis

Project description:Centriolar satellites are multiprotein aggregates that orbit the centrosome and govern centrosome homeostasis and primary cilia formation. In contrast to the scaffold PCM1, which nucleates centriolar satellites and has been linked to microtubule dynamics, autophagy, and intracellular trafficking, the functions of its close interactant CEP131 beyond ciliogenesis remain unclear. By using a knockout strategy in a T-cell line unable to form primary cilia, we report that, although dispensable for centriolar satellite assembly, CEP131 participates in optimal tubulin modifications and microtubule regrowth. Our unsupervised label-free proteomic analysis by quantitative mass spectrometry further uncovered both a mitochondrial and an anti-apoptotic signature. Without CEP131, mitochondria showed increased respiration and formed a more elongated network. In response to cell death inducers converging on mitochondria, knockout cells displayed delayed cytochrome c release from mitochondria, subsequent caspases activation, and ultimately in apoptosis. This defect in mitochondrial permeabilization was intrinsic as it could be recapitulated in vitro with isolated organelles. Together, these data extend the functions of CEP131 to life-and-death decisions and propose ways to interfere with mitochondrial apoptosis.

2024-01-26 | PXD042470 | 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