scholarly journals Uptake and Fate of Extracellular Membrane Vesicles: Nucleoplasmic Reticulum-Associated Late Endosomes as a New Gate to Intercellular Communication

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1931 ◽  
Author(s):  
Denis Corbeil ◽  
Mark F. Santos ◽  
Jana Karbanová ◽  
Thomas Kurth ◽  
Germana Rappa ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Cellular Response ◽  
Protein A ◽  
Membrane Vesicles ◽  
Small Gtpase ◽  
Host Cells ◽  
Biological Information ◽  
Late Endosomes ◽  
Donor Cells ◽  
Nucleoplasmic Reticulum

Extracellular membrane vesicles (EVs) are emerging as new vehicles in intercellular communication, but how the biological information contained in EVs is shared between cells remains elusive. Several mechanisms have been described to explain their release from donor cells and the initial step of their uptake by recipient cells, which triggers a cellular response. Yet, the intracellular routes and subcellular fate of EV content upon internalization remain poorly characterized. This is particularly true for EV-associated proteins and nucleic acids that shuttle to the nucleus of host cells. In this review, we will describe and discuss the release of EVs from donor cells, their uptake by recipient cells, and the fate of their cargoes, focusing on a novel intracellular route wherein small GTPase Rab7+ late endosomes containing endocytosed EVs enter into nuclear envelope invaginations and deliver their cargo components to the nucleoplasm of recipient cells. A tripartite protein complex composed of (VAMP)-associated protein A (VAP-A), oxysterol-binding protein (OSBP)-related protein-3 (ORP3), and Rab7 is essential for the transfer of EV-derived components to the nuclear compartment by orchestrating the particular localization of late endosomes in the nucleoplasmic reticulum.

scholarly journals Lack of Outer Membrane Protein A Enhances the Release of Outer Membrane Vesicles and Survival ofVibrio choleraeand Suppresses Viability ofAcanthamoeba castellanii

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Soni Priya Valeru ◽  
Salah Shanan ◽  
Haifa Alossimi ◽  
Amir Saeed ◽  
Gunnar Sandström ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Outer Membrane Proteins ◽  
Protein A ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Wild Type ◽  
Outer Membrane Protein A

Vibrio cholerae, the causative agent of the diarrhoeal disease cholera, survives in aquatic environments. The bacterium has developed a survival strategy to grow and survive insideAcanthamoeba castellanii. It has been shown thatV. choleraeexpresses outer membrane proteins as virulence factors playing a role in the adherence to interacted host cells. This study examined the role of outer membrane protein A (OmpA) and outer membrane vesicles (OMVs) in survival ofV. choleraealone and during its interaction withA. castellanii. The results showed that anOmpAmutant ofV. choleraesurvived longer than wild-typeV. choleraewhen cultivated alone. Cocultivation withA. castellaniienhanced the survival of both bacterial strains andOmpAprotein exhibited no effect on attachment, engulfment, and survival inside the amoebae. However, cocultivation of theOmpAmutant ofV. choleraedecreased the viability ofA. castellaniiand this bacterial strain released more OMVs than wild-typeV. cholerae. Surprisingly, treatment of amoeba cells with OMVs isolated from theOmpAmutant significantly decreased viable counts of the amoeba cells. In conclusion, the results might highlight a regulating rule forOmpAin survival ofV. choleraeand OMVs as a potent virulence factor for this bacterium towards eukaryotes in the environment.

scholarly journals VAMP-associated protein-A and oxysterol-binding protein–related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum

2018 ◽  
Vol 293 (36) ◽  
pp. 13834-13848 ◽  
Author(s):  
Mark F. Santos ◽  
Germana Rappa ◽  
Jana Karbanová ◽  
Thomas Kurth ◽  
Denis Corbeil ◽  
...  
Keyword(s):  
Binding Protein ◽  
Protein A ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Late Endosomes ◽  
Nucleoplasmic Reticulum

scholarly journals Burkholderia cenocepacia transcriptome during the early contacts with giant plasma membrane vesicles derived from live bronchial epithelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andreia I. Pimenta ◽  
Nuno Bernardes ◽  
Marta M. Alves ◽  
Dalila Mil-Homens ◽  
Arsenio M. Fialho
Keyword(s):  
Membrane Vesicles ◽  
Bronchial Epithelial Cell ◽  
Host Cells ◽  
Burkholderia Cenocepacia ◽  
Transport Systems ◽  
Epithelial Cell Line ◽  
Plasma Membrane Vesicles ◽  
Bronchial Epithelial ◽  
Cellular Processes ◽  
Associated Functions

AbstractBurkholderia cenocepacia is known for its capacity of adherence and interaction with the host, causing severe opportunistic lung infections in cystic fibrosis patients. In this work we produced Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line and validated their use as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia. RNA-sequencing was performed and the analysis of the B. cenocepacia K56-2 transcriptome after the first contacts with the surface of host cells allowed the recognition of genes implicated in bacterial adaptation and virulence-associated functions. The sensing of host membranes led to a transcriptional shift that caused a cascade of metabolic and physiological adaptations to the host specific environment. Many of the differentially expressed genes encode proteins related with central metabolic pathways, transport systems, cellular processes, and virulence traits. The understanding of the changes in gene expression that occur in the early steps of infection can uncover new proteins implicated in B. cenocepacia-host cell adhesion, against which new blocking agents could be designed to control the progression of the infectious process.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas M. Negretti ◽  
Christopher R. Gourley ◽  
Prabhat K. Talukdar ◽  
Geremy Clair ◽  
Courtney M. Klappenbach ◽  
...  
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Small Gtpase ◽  
Host Cells ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Cell Binding ◽  
Actin Reorganization ◽  
Cell Cytosol

AbstractCampylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

scholarly journals A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 601
Author(s):  
Yu-Jing Zeng ◽  
Min-Kung Hsu ◽  
Chiao-An Tsai ◽  
Chun-Yen Chu ◽  
Hsing-Chieh Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cellular Response ◽  
Cell Clone ◽  
Fever Virus ◽  
Gene Set Enrichment Analysis ◽  
Host Cells ◽  
Scale Production ◽  
Bovine Ephemeral Fever Virus ◽  
Virus Growth ◽  
Bovine Ephemeral Fever

During industrial-scale production of viruses for vaccine manufacturing, anti-viral response of host cells can dampen maximal viral antigen yield. In addition to interferon responses, many other cellular responses, such as the AMPK signaling pathway or senescence-like response may inhibit or slow down virus amplification in the cell culture system. In this study, we first performed a Gene Set Enrichment Analysis of the whole-genome mRNA transcriptome and found a senescence-like cellular response in BHK-21 cells when infected with bovine ephemeral fever virus (BEFV). To demonstrate that this senescence-like state may reduce virus growth, BHK-21 subclones showing varying degrees of a senescence-like state were infected with BEFV. The results showed that the BHK-21 subclones showing high senescence staining could inhibit BEFV replication while low senescence-staining subclones are permissive to virus replication. Using a different approach, a senescence-like state was induced in BHK-21 using a small molecule, camptothecin (CPT), and BEFV susceptibility were examined. The results showed that CPT-treated BHK-21 is more resistant to virus infection. Overall, these results indicate that a senescence-like response may be at play in BHK-21 upon virus infection. Furthermore, cell clone selection and modulating treatments using small molecules may be tools in countering anti-viral responses.

Replication Protein A phosphorylation and the cellular response to DNA damage

DNA Repair ◽  
2004 ◽  
Vol 3 (8-9) ◽  
pp. 1015-1024 ◽  
Author(s):  
Sara K. Binz ◽  
Anne M. Sheehan ◽  
Marc S. Wold
Keyword(s):  
Dna Damage ◽  
Cellular Response ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein

scholarly journals Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells

2012 ◽  
Vol 80 (11) ◽  
pp. 3748-3760 ◽  
Author(s):  
Nore Ojogun ◽  
Amandeep Kahlon ◽  
Stephanie A. Ragland ◽  
Matthew J. Troese ◽  
Juliana E. Mastronunzio ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Anaplasma Phagocytophilum ◽  
Protein A ◽  
Host Cells ◽  
Mammalian Host ◽  
Content Type ◽  
Outer Membrane Protein A ◽  
Sialylated Glycoproteins

ABSTRACTAnaplasma phagocytophilumis the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis (HGA).A. phagocytophilumbinding to sialyl Lewis x (sLex) and other sialylated glycans that decorate P selectin glycoprotein 1 (PSGL-1) and other glycoproteins is critical for infection of mammalian host cells. Here, we demonstrate the importance ofA. phagocytophilumouter membrane protein A (OmpA) APH_0338 in infection of mammalian host cells. OmpA is transcriptionally induced during transmission feeding ofA. phagocytophilum-infected ticks on mice and is upregulated during invasion of HL-60 cells. OmpA is presented on the pathogen's surface. Sera from HGA patients and experimentally infected mice recognize recombinant OmpA. Pretreatment ofA. phagocytophilumorganisms with OmpA antiserum reduces their abilities to infect HL-60 cells. The OmpA N-terminal region is predicted to contain the protein's extracellular domain. GlutathioneS-transferase (GST)-tagged versions of OmpA and OmpA amino acids 19 to 74 (OmpA19-74) but not OmpA75-205bind to, and competitively inhibitA. phagocytophiluminfection of, host cells. Pretreatment of host cells with sialidase or trypsin reduces or nearly eliminates, respectively, GST-OmpA adhesion. Therefore, OmpA interacts with sialylated glycoproteins. This study identifies the firstA. phagocytophilumadhesin-receptor pair and delineates the region of OmpA that is critical for infection.

scholarly journals Aggregatibacter actinomycetemcomitans Leukotoxin Is Delivered to Host Cells in an LFA-1-Indepdendent Manner When Associated with Outer Membrane Vesicles

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 414 ◽  
Author(s):  
Justin Nice ◽  
Nataliya Balashova ◽  
Scott Kachlany ◽  
Evan Koufos ◽  
Eric Krueger ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Aggressive Periodontitis ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Type I ◽  
Outer Membranes ◽  
Independent Mechanism ◽  
Bacterial Outer Membrane

The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, has been associated with localized aggressive periodontitis (LAP). In particular, highly leukotoxic strains of A. actinomycetemcomitans have been more closely associated with this disease, suggesting that LtxA is a key virulence factor for A. actinomycetemcomitans. LtxA is secreted across both the inner and outer membranes via the Type I secretion system, but has also been found to be enriched within outer membrane vesicles (OMVs), derived from the bacterial outer membrane. We have characterized the association of LtxA with OMVs produced by the highly leukotoxic strain, JP2, and investigated the interaction of these OMVs with host cells to understand how LtxA is delivered to host cells in this OMV-associated form. Our results demonstrated that a significant fraction of the secreted LtxA exists in an OMV-associated form. Furthermore, we have discovered that in this OMV-associated form, the toxin is trafficked to host cells by a cholesterol- and receptor-independent mechanism in contrast to the mechanism by which free LtxA is delivered. Because OMV-associated toxin is trafficked to host cells in an entirely different manner than free toxin, this study highlights the importance of studying both free and OMV-associated forms of LtxA to understand A. actinomycetemcomitans virulence.

scholarly journals Trafficking of prion proteins through a caveolae-mediated endosomal pathway

2003 ◽  
Vol 162 (4) ◽  
pp. 703-717 ◽  
Author(s):  
Peter J. Peters ◽  
Alexander Mironov ◽  
David Peretz ◽  
Elly van Donselaar ◽  
Estelle Leclerc ◽  
...  
Keyword(s):  
Prion Proteins ◽  
Protein A ◽  
Subcellular Location ◽  
Cellular Prion Protein ◽  
Endocytic Pathway ◽  
Live Cells ◽  
Trafficking Pathway ◽  
Late Endosomes ◽  
Endosomal Pathway ◽  
Glycosylphosphatidyl Inositol

To understand the posttranslational conversion of the cellular prion protein (PrPC) to its pathologic conformation, it is important to define the intracellular trafficking pathway of PrPC within the endomembrane system. We studied the localization and internalization of PrPC in CHO cells using cryoimmunogold electron microscopy. At steady state, PrPC was enriched in caveolae both at the TGN and plasma membrane and in interconnecting chains of endocytic caveolae. Protein A–gold particles bound specifically to PrPC on live cells. These complexes were delivered via caveolae to the pericentriolar region and via nonclassical, caveolae-containing early endocytic structures to late endosomes/lysosomes, thereby bypassing the internalization pathway mediated by clathrin-coated vesicles. Endocytosed PrPC-containing caveolae were not directed to the ER and Golgi complex. Uptake of caveolae and degradation of PrPC was slow and sensitive to filipin. This caveolae-dependent endocytic pathway was not observed for several other glycosylphosphatidyl inositol (GPI)-anchored proteins. We propose that this nonclassical endocytic pathway is likely to determine the subcellular location of PrPC conversion.

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