Biology of the Cell最新文献

{"title":"Extracellular vesicles containing the I-BAR protein IRSp53 are released from the cell plasma membrane in an Arp2/3 dependent manner","authors":"Aurore de Poret,&nbsp;Rayane Dibsy,&nbsp;Peggy Merida,&nbsp;Alice Trausch,&nbsp;Kaushik Inamdar,&nbsp;Delphine Muriaux","doi":"10.1111/boc.202100095","DOIUrl":"10.1111/boc.202100095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgroud</h3>\u0000 \u0000 <p>Extracellular vesicles (EVs) are nanometric membrane vesicles produced by cells and involved in cell–cell communication. EV formation can occur in endosomal compartments whose budding depends on the ESCRT machinery (i.e., exosomes), or at the cell plasma membrane (i.e., EVs or microvesicles). How these EVs bud from the cell plasma membrane is not completely understood. Membrane curvatures of the plasma membrane toward the exterior are often generated by I-BAR domain proteins. I-BAR proteins are cytosolic proteins that when activated bind to the cell plasma membrane and are involved in protrusion formation including filopodia and lamellipodia. These proteins contain a conserved I-BAR domain that senses curvature and induces negative membrane curvatures at the plasma membrane. I-BAR proteins, such as IRSp53, also interact with actin co-factors to favor membrane protrusions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we explore whether the I-BAR protein IRSp53 is sorting with EVs and if ectopic GFP-tagged I-BAR proteins, such as IRSp53-GFP, as well as related IRTKS-GFP or Pinkbar proteins, can be found in these EVs originated from the cell plasma membrane. We found that a subpopulation of these I-BAR EVs, which are negative for the CD81 exosomal biomarker, are produced from the cell plasma membrane in a TSG101-independent manner but in an Arp2/3-dependent manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results thus reveal that IRSp53 containing EVs represent a subset of plasma membrane EVs whose production depends on branched actin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>IRSp53 belongs to the I-BAR family proteins involved in curving cell membranes through a link with cortical actin. In that perspective, IRSp53 was shown to help membrane curvature of HIV-1 particles and, here, to be part of the budding process of a sub-population of EVs through its link with Arp2/3. IRSp53 is consequently a biomarker of these EVs of the cell plasma membrane.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 10","pages":"259-275"},"PeriodicalIF":2.7,"publicationDate":"2022-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202100095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40597414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 Nef hijacks both exocytic and endocytic pathways of host intracellular trafficking through differential regulation of Rab GTPases","authors":"Sushila Kumari,&nbsp;Prasanta K. Dash,&nbsp;Tripti Kumari,&nbsp;Ming-Lei Guo,&nbsp;Jimut Kanti Ghosh,&nbsp;Shilpa J. Buch,&nbsp;Raj Kamal Tripathi","doi":"10.1111/boc.202100027","DOIUrl":"10.1111/boc.202100027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>HIV-1 Nef regulates several cellular functions in an infected cell which results in viral persistence and AIDS pathogenesis. The currently understood molecular mechanism(s) underlying Nef-dependent cellular function(s) are unable to explain how events are coordinately regulated in the host cell. Intracellular membranous trafficking maintains cellular homeostasis and is regulated by Rab GTPases - a member of the Ras superfamily.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the current study, we tried to decipher the role of Nef on the Rab GTPases-dependent complex and vesicular trafficking. Expression profiling of Rabs in Nef-expressing cells showed that Nef differentially regulates the expression of individual Rabs in a cell-specific manner. Further analysis of Rabs in HIV-1_NL4-3 or ΔNef infected cells demonstrated that the Nef protein is responsible for variation in Rabs expression. Using a panel of competitive peptide inhibitors against Nef, we identified the critical domain of HIV-1 Nef involved in modulation of Rabs expression. The molecular function of Nef-mediated upregulation of Rab5 and Rab7 and downregulation of Rab11 increased the transport of SERINC5 from the cell surface to the lysosomal compartment. Moreover, the Nef-dependent increase in Rab27 expression assists exosome release. Reversal of Rabs expression using competitive inhibitors against Nef and manipulation of Rabs expression reduced viral release and infectivity of progeny virions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that Nef differentially regulates the expression of Rab proteins in HIV-1 infected cells to hijack the host intracellular trafficking, which augments viral replication and HIV-1 pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Our study emphasized the indispensable role of HIV-1 protein Nef on various aspects of the intracellular trafficking regulated by Rabs GTPases, which explained how HIV-1 Nef may hijack membrane trafficking pathways in infected cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 10","pages":"276-292"},"PeriodicalIF":2.7,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49220431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizure classification with selected frequency bands and EEG montages: a Natural Language Processing approach.","authors":"Ziwei Wang, Paolo Mengoni","doi":"10.1186/s40708-022-00159-3","DOIUrl":"10.1186/s40708-022-00159-3","url":null,"abstract":"<p><p>Individualized treatment is crucial for epileptic patients with different types of seizures. The differences among patients impact the drug choice as well as the surgery procedure. With the advance in machine learning, automatic seizure detection can ease the manual time-consuming and labor-intensive procedure for diagnose seizure in the clinical setting. In this paper, we present an electroencephalography (EEG) frequency bands (sub-bands) and montages selection (sub-zones) method for classifier training that exploits Natural Language Processing from individual patients' clinical report. The proposed approach is targeting for individualized treatment. We integrated the prior knowledge from patient's reports into the classifier-building process, mimicking the authentic thinking process of experienced neurologist's when diagnosing seizure using EEG. The keywords from clinical documents are mapped to the EEG data in terms of frequency bands and scalp EEG electrodes. The data of experiments are from the Temple University Hospital EEG seizure corpus, and the dataset is divided based on each group of patients with same seizure type and same recording electrode references. The classifier includes Random Forest, Support Vector Machine and Multi-Layer Perceptron. The classification performance indicates that competitive results can be achieve with a small portion of EEG the data. Using the sub-zones selection for Generalized Seizures (GNSZ) on all three electrodes, data are reduced by nearly 50% while the performance metrics remain at the same level with the whole frequency and zones. Moreover, when selecting by sub-zones and sub-bands together for GNSZ with Linked Ears reference, the data range reduced to 0.3% of whole range, and the performance deviates less than 3% from the results with whole range of data. Results show that using proposed approach may lead to more efficient implementations of the seizure classifier to be executed on power-efficient devices for long lasting real-time seizures detection.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"91 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77985993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-density cell culture enhances hepatic function through tight junction formation in HepG2 cells","authors":"Rieko Tanaka-Yachi,&nbsp;Kazuko Aizawa,&nbsp;Kie shimizu,&nbsp;Hidenori Akutsu,&nbsp;Kazuaki Nakamura","doi":"10.1111/boc.202200002","DOIUrl":"10.1111/boc.202200002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>An in vitro evaluation system using cultured hepatocytes is the most useful method in preclinical research, such as drug metabolism and toxicity test. Human hepatocytes should be used in an in vitro evaluation system because the expression of drug-metabolizing enzymes varies among animal species. HepG2 cells, a liver cancer-derived cell line, are widely used as a human hepatocyte model; however, their hepatic functions are generally weak.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we showed that low-density HepG2 cell culture induces hepatic function. The morphology of HepG2 cells was altered depending on the cell density at the time of seeding. Low-density cultured HepG2 cells proliferated as tightly packed colonies. The HepG2 cell colonies in low-density culture demonstrated enhanced tight junction formation. Tight junction protein gene expression levels, such as those of zonula occludens-1 (ZO-1), junctional adhesion molecule 1 (JAM), claudin, occludin, and tricellulin, increased in low-density cultured HepG2 cells. Phases I and II metabolic enzymes, phase III transporter gene expression, and CYP3A4 activity also increased in low-density cultured HepG2 cells. Occludin and tricellulin knockdown inhibited the increased hepatic function in low-density cultures. Tricellulin knockdown reduced the expression of hepatocyte nuclear factor 6 (HNF6), CCAAT/enhancer-binding protein alpha (CEBPA), and aryl hydrocarbon receptor (AHR). In addition, the expression of nuclear receptor subfamily 1 group h member 2 (NR1H2) increased in low-density cultures, canceled by occludin and tricellulin knockdown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that low-density HepG2 cell cultures enhance hepatic function by promoting tight junction formation and demonstrate the importance of cell density in drug evaluation using hepatocyte cell lines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 9","pages":"225-236"},"PeriodicalIF":2.7,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44946835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordination between phospholipid pools and DNA damage sensing","authors":"Sara Ovejero,&nbsp;Caroline Soulet,&nbsp;Sylvain Kumanski,&nbsp;María Moriel-Carretero","doi":"10.1111/boc.202200007","DOIUrl":"10.1111/boc.202200007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Both phospholipid synthesis and the detection of DNA damage are coupled to cell cycle progression, yet whether these two aspects crosstalk to each other remains unassessed. We postulate here that shortage of phospholipids, which negatively affects proliferation, may reduce the need for checkpoint activation in response to DNA damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>To test this hypothesis, we explore here the DNA Damage Response activation in response to seven different genotoxins, in three distinct cell types, and manipulate phospholipid synthesis both pharmacologically and genetically. This allows us to point at the DNA damage response kinase ATR as responsible for the coordination between phospholipid levels and DNA damage sensing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Significance</h3>\u0000 \u0000 <p>ATR could combine its ability to sense DNA damage and phospholipid profiles in order to finetune the response to DNA lesions depending on metabolic cues. Further, our analysis reveals the functional significance of this crosstalk to keep genome homeostasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 8","pages":"211-219"},"PeriodicalIF":2.7,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45464113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D FIB-SEM structural insights into the architecture of sub-pellicular microtubules of Trypanosoma cruzi epimastigotes","authors":"Juliana C. Vidal,&nbsp;Wanderley De Souza","doi":"10.1111/boc.202100038","DOIUrl":"10.1111/boc.202100038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background information</h3>\u0000 \u0000 <p>Trypanosomatidae, which includes eukaryotic species agents of diseases like leishmaniasis, sleeping sickness, and Chagas disease, have special structures and organelles not found in mammalian cells. They present a layer of microtubules, known as subpellicular microtubules (SPMT), located underneath the plasma membrane and responsible for preserving cell morphology, cell polarity, the position of single copy organelles, and morphological changes that occur throughout the protozoan life cycle. Even though a lot of knowledge about the SPMT is available, we still do not know exactly how each microtubule in the system is organized in three dimensions. Here, we use focused ion beam scanning electron microscopy (FIB-SEM) to analyze the tridimensional organization of epimastigotes SPMT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The high-resolution 3D analyses revealed that certain microtubules of the SPMT end more prematurely than the neighboring ones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These microtubules could (1) be shorter or (2) have the same length as the neighboring ones, assuming that those end up earlier at their other end, might be treadmilling/catastrophe events that have not yet been described in trypanosomatids.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 8","pages":"203-210"},"PeriodicalIF":2.7,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42169065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of Andrée Tixier-Vidal (1923–2021) to modern cell biology","authors":"Claude Tougard,&nbsp;Thierry Galli,&nbsp;Bruno Goud","doi":"10.1111/boc.202200020","DOIUrl":"10.1111/boc.202200020","url":null,"abstract":"<p>This article illustrates the main stages of the scientific career of Dr Andrée Tixier–Vidal, a pioneer in cell biology research in France. She made important discoveries in the field of hormone secretion and neuronal morphogenesis. She played a key role in developing pituitary and neuronal cultures and using electron microscopy to study cellular structures. Her scientific influence continues to irradiate through her students and collaborators.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 7","pages":"181-184"},"PeriodicalIF":2.7,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42941478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The magic of MAGI-1: A scaffolding protein with multi signalosomes and functional plasticity","authors":"Katherine J. D. A. Excoffon,&nbsp;Christina L. Avila,&nbsp;Mahmoud S. Alghamri,&nbsp;Abimbola O. Kolawole","doi":"10.1111/boc.202200014","DOIUrl":"10.1111/boc.202200014","url":null,"abstract":"<p>MAGI-1 is a critical cellular scaffolding protein with over 110 different cellular and microbial protein interactors. Since the discovery of MAGI-1 in 1997, MAGI-1 has been implicated in diverse cellular functions such as polarity, cell–cell communication, neurological processes, kidney function, and a host of diseases including cancer and microbial infection. Additionally, MAGI-1 has undergone nomenclature changes in response to the discovery of an additional PDZ domain, leading to lack of continuity in the literature. We address the nomenclature of MAGI-1 as well as summarize many of the critical functions of the known interactions. Given the importance of many of the interactors, such as human papillomavirus E6, the Coxsackievirus and adenovirus receptor (CAR), and PTEN, the enhancement or disruption of MAGI-based interactions has the potential to affect cellular functions that can potentially be harnessed as a therapeutic strategy for a variety of diseases.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 7","pages":"185-198"},"PeriodicalIF":2.7,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-specific N-glycan profiles of α5β1 integrin from rat liver","authors":"Ekaterina Mirgorodskaya,&nbsp;Estelle Dransart,&nbsp;Massiullah Shafaq-Zadah,&nbsp;Daniel Roderer,&nbsp;Carina Sihlbom,&nbsp;Hakon Leffler,&nbsp;Ludger Johannes","doi":"10.1111/boc.202200017","DOIUrl":"10.1111/boc.202200017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Like most other cell surface proteins, α₅β₁ integrin is glycosylated, which is required for its various activities in ways that mostly remain to be determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we have established the first comprehensive site-specific glycan map of α₅β₁ integrin that was purified from a natural source, that is, rat liver. This analysis revealed striking site selective variations in glycan composition. Complex bi, tri, or tetraantennary <i>N</i>-glycans were predominant at various proportions at most potential <i>N</i>-glycosylation sites. A few of these sites were nonglycosylated or contained high mannose or hybrid glycans, indicating that early <i>N-</i>glycan processing was hindered. Almost all complex <i>N-</i>glycans had fully galactosylated and sialylated antennae. Moderate levels of core fucosylation and high levels of O-acetylation of NeuAc residues were observed at certain sites. An O-linked HexNAc was found in an EGF-like domain of β₁ integrin. The extensive glycan information that results from our study was projected onto a map of α₅β₁ integrin that was obtained by homology modeling. We have used this model for the discussion of how glycosylation might be used in the functional cycle of α₅β₁ integrin. A striking example concerns the involvement of glycan-binding galectins in the regulation of the molecular homeostasis of glycoproteins at the cell surface through the formation of lattices or endocytic pits according to the glycolipid-lectin (GL-Lect) hypothesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We expect that the glycoproteomics data of the current study will serve as a resource for the exploration of structural mechanisms by which glycans control α₅β₁ integrin activity and endocytic trafficking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Glycosylation of α₅β₁ integrin has been implicated in multiple aspects of integrin function and structure. Yet, detailed knowledge of its glycosylation, notably the specific sites of glycosylation, is lacking. Furthermore, the α₅β₁ integrin preparation that was analyzed here is from a natural source, which is of importance as there is not a lot of literature in the field about the glycosylation of “native” glycoproteins.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 6","pages":"160-176"},"PeriodicalIF":2.7,"publicationDate":"2022-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45802042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide increases exosomes secretion from endothelial progenitor cells by toll-like receptor 4 dependent mechanism","authors":"Liang Xia,&nbsp;Xiaotian Wang,&nbsp;Weidong Yao,&nbsp;Meihui Wang,&nbsp;Junhui Zhu","doi":"10.1111/boc.202100086","DOIUrl":"10.1111/boc.202100086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Endothelial progenitor cells (EPCs) can exert angiogenic effects by a paracrine mechanism, where exosomes work as an important mediator. Recent studies reported functional expression of toll-like receptor (TLR) 4 on human EPCs and dose-dependent effects of lipopolysaccharide (LPS) on EPC angiogenic properties. To study the effects of TLR4/LPS signaling on EPC-derived exosomes (Exo) and clarify the mechanism, we investigated the role of LPS on exosomes secretion from human EPCs and tested their anti-oxidation/senescence functions. We employed the inhibitors of the plasma membrane Ca²⁺-ATPase (PMCA), endoplasmic reticulum Ca²⁺-ATPase (ERCA), PLC-IP₃ pathway and store-operated calcium entry to assess the effects of LPS on EPC intracellular calcium signalings which critical for exosome secretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LPS induced the release of Exo in a TLR4-dependent manner in vitro, which effect can be partly abrogated by an membrane-permeable IP ₃ R antagonist, 2-aminoethyl diphenylborinate (2-APB), but not PLC inhibitor, U-73122. The LPS can significantly delay the fallback of [Ca²⁺]i after isolating the cellular PMCA activity, and disturb PMCA 1/4 expression. The distribution of elevated intracellular calcium seemed coincident with the development of the multivesicular bodies (MVBs). furthermore, the anti-oxidation/senescence properties of LPS-induced Exo were validated by the senescence-associated β-galactosidase activity assay and reactive oxygen species (ROS) related H₂DCF-DA assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The mechanism of PMCA downregulation and IP₃R-dependent ER Ca²⁺ release may contribute to the pro-exosomal effects of LPS on EPCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study provides new insights into the potential role of LPS/TLR4 pathway in regulating EPC-derived exosomes, which may help to develop some feasible approach to manipulate the Exo secretion and promote the clinical application of EPCs therapy in future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 5","pages":"127-137"},"PeriodicalIF":2.7,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46757185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}