Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Centrosome, the Newly Identified Passenger through Tunneling Nanotubes, Increases Binucleation and Proliferation Marker in Receiving Cells.

ABSTRACT: Type 1 tunneling nanotubes (TNTs-1) are long, cytoplasmic protrusions containing actin, microtubules and intermediate filaments that provide a bi-directional road for the transport of various components between distant cells. TNT-1 formation is accompanied by dramatic cytoskeletal reorganization offering mechanical support for intercellular communication. Although the centrosome is the major microtubule nucleating center and also a signaling hub, the relationship between the centrosome and TNTs-1 is still unexplored. We provide here the first evidence of centrosome localization and orientation towards the TNTs-1 protrusion site, which is implicated in TNT-1 formation. We also envision a model whereby synchronized reorientation of the Golgi apparatus along with the centrosome towards TNTs-1 ensures effective polarized trafficking through TNTs-1. Furthermore, using immunohistochemistry and live imaging, we observed for the first time the movement of an extra centrosome within TNTs-1. In this regard, we hypothesize a novel role for TNTs-1 as a critical pathway serving to displace extra centrosomes and potentially to either protect malignant cells against aberrant centrosome amplification or contribute to altering cells in the tumor environment. Indeed, we have observed the increase in binucleation and proliferation markers in receiving cells. The fact that the centrosome can be both as the base and the user of TNTs-1 offers new perspectives and new opportunities to follow in order to improve our knowledge of the pathophysiological mechanisms under TNT control.

SUBMITTER: Dubois F

PROVIDER: S-EPMC8467045 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Microglia care for neurons through tunneling nanotubes

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-01 | GSE209972 | GEO

Cdk4 and nek2 signal binucleation and centrosome amplification in a her2+ breast cancer model.

Project description:Centrosome amplification (CA) is a contributor to carcinogenesis, generating aneuploidy, and chromosome instability. Previous work shows that breast adenocarcinomas have a higher frequency of centrosome defects compared to normal breast tissues. Abnormal centrosome phenotypes are found in pre-malignant lesions, suggesting an early role in breast carcinogenesis. However, the role of CA in breast cancers remains elusive. Identification of pathways and regulatory molecules involved in the generation of CA is essential to understanding its role in breast tumorigenesis. We established a breast cancer model of CA using Her2-positive cells. Our goal was to identify centrosome cycle molecules that are deregulated by aberrant Her2 signaling and the mechanisms driving CA. Our results show some Her2+ breast cancer cell lines harbor both CA and binucleation. Abolishing the expression of Cdk4 abrogated both CA and binucleation in these cells. We also found the source of binucleation in these cells to be defective cytokinesis that is normalized by downregulation of Cdk4. Protein levels of Nek2 diminish upon Cdk4 knockdown and vice versa, suggesting a molecular connection between Cdk4 and Nek2. Knockdown of Nek2 reduces CA and binucleation in this model while its overexpression further enhances centrosome amplification. We conclude that CA is modulated through Cdk4 and Nek2 signaling and that binucleation is a likely source of CA in Her2+ breast cancer cells.

| S-EPMC3679029 | biostudies-literature

Pretransplant Midodrine Use: A Newly Identified Risk Marker for Complications After Kidney Transplantation.

Project description:Midodrine is prescribed to prevent symptomatic hypotension and decrease complications associated with hypotension during dialysis. We hypothesized that midodrine use before kidney transplantation may be a novel marker for posttransplant risk.We analyzed integrated national US transplant registry, pharmacy records, and Medicare claims data for 16 308 kidney transplant recipients transplanted 2006 to 2008, of whom 308 (1.9%) had filled midodrine prescriptions in the year before transplantation. Delayed graft function (DGF), graft failure, and patient death were ascertained from the registry. Posttransplant cardiovascular complications were identified using diagnosis codes on Medicare billing claims. Adjusted associations of pretransplant midodrine use with complications at 3 and 12 months posttransplant were quantified by multivariate Cox or logistic regression, including propensity for midodrine exposure.At 3 months, patients who used midodrine pretransplant had significantly (P < 0.05) higher rates of DGF, 32% versus 19%; hypotension, 14% versus 4%; acute myocardial infarction, 4% versus 2%; cardiac arrest, 2% versus 0.9%, graft failure, 5% versus 2%; and death, 4% versus 1% than nonusers. After multivariate adjustment including recipient and donor factors, as well as for the propensity of midodrine exposure, pretransplant midodrine use was independently associated with risks of DGF (adjusted odds ratio, 1.78; 95% confidence interval [CI], 1.36-2.32), and 3 month death-censored graft failure (adjusted hazard ratio, 2.0; 95% CI, 1.18-3.39), and death (adjusted hazard ratio, 3.49; 95% CI, 1.95-6.24). Patterns were similar at 12 months.Although associations may in part reflect underlying conditions, the need for midodrine before kidney transplantation is a risk marker for complications including DGF, graft failure, and death.

| S-EPMC4846474 | biostudies-literature

Microglia care for neurons through tunneling nanotubes [Dataset 2 Microglia mRNA-seq]

Project description:We report the transfer of alpha-s-ynuclein aggregates from neurons to microglia and examined transcriptomic changes following protein extraction. By obtaining RNA samples, we performed differential expression analysis and generated gene ontology enrichment and network analysis.

2023-12-01 | GSE209971 | GEO

Microglia care for neurons through tunneling nanotubes [Dataset 1 Neurons mRNA-seq]

2023-12-01 | GSE209970 | GEO

Prion aggregates transfer through tunneling nanotubes in endocytic vesicles.

Project description:Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases caused by the misfolding of the cellular prion protein to an infectious form PrP(Sc). The intercellular transfer of PrP(Sc) is a question of immediate interest as the cell-to-cell movement of the infectious particle causes the inexorable propagation of disease. We have previously identified tunneling nanotubes (TNTs) as one mechanism by which PrP(Sc) can move between cells. Here we investigate further the details of this mechanism and show that PrP(Sc) travels within TNTs in endolysosomal vesicles. Additionally we show that prion infection of CAD cells increases both the number of TNTs and intercellular transfer of membranous vesicles, thereby possibly playing an active role in its own intercellular transfer via TNTs.

| S-EPMC4601206 | biostudies-literature

Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes.

Project description:Many lines of evidence suggest that the Parkinson's disease (PD)-related protein ?-synuclein (?-SYN) can propagate from cell to cell in a prion-like manner. However, the cellular mechanisms behind the spreading remain elusive. Here, we show that human astrocytes derived from embryonic stem cells actively transfer aggregated ?-SYN to nearby astrocytes via direct contact and tunneling nanotubes (TNTs). Failure in the astrocytes' lysosomal digestion of excess ?-SYN oligomers results in ?-SYN deposits in the trans-Golgi network followed by endoplasmic reticulum swelling and mitochondrial disturbances. The stressed astrocytes respond by conspicuously sending out TNTs, enabling intercellular transfer of ?-SYN to healthy astrocytes, which in return deliver mitochondria, indicating a TNT-mediated rescue mechanism. Using a pharmacological approach to inhibit TNT formation, we abolished the transfer of both ?-SYN and mitochondria. Together, our results highlight the role of astrocytes in ?-SYN cell-to-cell transfer, identifying possible pathophysiological events in the PD brain that could be of therapeutic relevance.SIGNIFICANCE STATEMENT Astrocytes are the major cell type in the brain, yet their role in Parkinson's disease progression remains elusive. Here, we show that human astrocytes actively transfer aggregated ?-synuclein (?-SYN) to healthy astrocytes via direct contact and tunneling nanotubes (TNTs), rather than degrade it. The astrocytes engulf large amounts of oligomeric ?-SYN that are subsequently stored in the trans-Golgi network region. The accumulation of ?-SYN in the astrocytes affects their lysosomal machinery and induces mitochondrial damage. The stressed astrocytes respond by sending out TNTs, enabling intercellular transfer of ?-SYN to healthy astrocytes. Our findings highlight an unexpected role of astrocytes in the propagation of ?-SYN pathology via TNTs, revealing astrocytes as a potential target for therapeutic intervention.

| S-EPMC5719970 | biostudies-literature

Mycoplasma exploits mammalian tunneling nanotubes for cell-to-cell dissemination.

Project description:Using tunneling nanotubes (TNTs), various pathological molecules and viruses disseminate to adjacent cells intercellularly. Here, we show that the intracellular invasion of Mycoplasma hyorhinis induces the formation of actin- and tubulin-based TNTs in various mammalian cell lines. M. hyorhinis was found in TNTs generated by M. hyorhinis infection in NIH3T3 cells. Because mycoplasma-free recipient cells received mycoplasmas from M. hyorhinis-infected donor cells in a mixed co-culture system and not a spatially separated co-culture system, direct cell-to-cell contact via TNTs was necessary for the intracellular dissemination of M. hyorhinis. The activity of Rac1, which is a small GTP binding protein, was increased by the intracellular invasion of M. hyorhinis, and its pharmacological and genetic inhibition prevented M. hyorhinis infection-induced TNT generation in NIH3T3 cells. The pharmacological and genetic inhibition of Rac1 also reduced the cell-to-cell dissemination of M. hyorhinis. Based on these data, we conclude that intracellular invasion of M. hyorhinis induces the formation of TNTs, which are used for the cell-to-cell dissemination of M. hyorhinis. [BMB Reports 2019; 52(8): 490-495].

| S-EPMC6726209 | biostudies-literature

Tunneling nanotubes spread fibrillar ?-synuclein by intercellular trafficking of lysosomes.

Project description:Synucleinopathies such as Parkinson's disease are characterized by the pathological deposition of misfolded ?-synuclein aggregates into inclusions throughout the central and peripheral nervous system. Mounting evidence suggests that intercellular propagation of ?-synuclein aggregates may contribute to the neuropathology; however, the mechanism by which spread occurs is not fully understood. By using quantitative fluorescence microscopy with co-cultured neurons, here we show that ?-synuclein fibrils efficiently transfer from donor to acceptor cells through tunneling nanotubes (TNTs) inside lysosomal vesicles. Following transfer through TNTs, ?-synuclein fibrils are able to seed soluble ?-synuclein aggregation in the cytosol of acceptor cells. We propose that donor cells overloaded with ?-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. Our findings thus reveal a possible novel role of TNTs and lysosomes in the progression of synucleinopathies.

| S-EPMC5048354 | biostudies-literature

Influenza virus exploits tunneling nanotubes for cell-to-cell spread.

Project description:Tunneling nanotubes (TNTs) represent a novel route of intercellular communication. While previous work has shown that TNTs facilitate the exchange of viral or prion proteins from infected to naïve cells, it is not clear whether the viral genome is also transferred via this mechanism and further, whether transfer via this route can result in productive replication of the infectious agents in the recipient cell. Here we present evidence that lung epithelial cells are connected by TNTs, and in spite of the presence of neutralizing antibodies and an antiviral agent, Oseltamivir, influenza virus can exploit these networks to transfer viral proteins and genome from the infected to naïve cell, resulting in productive viral replication in the naïve cells. These observations indicate that influenza viruses can spread using these intercellular networks that connect epithelial cells, evading immune and antiviral defenses and provide an explanation for the incidence of influenza infections even in influenza-immune individuals and vaccine failures.

| S-EPMC5216422 | biostudies-literature

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