Ambra Pratelli, Dalia Corbo, Pietro Lupetti, Caterina Mencarelli
{"title":"The distal central pair segment is structurally specialised and contributes to IFT turnaround and assembly of the tip capping structures in Chlamydomonas flagella","authors":"Ambra Pratelli, Dalia Corbo, Pietro Lupetti, Caterina Mencarelli","doi":"10.1111/boc.202200038","DOIUrl":"10.1111/boc.202200038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Cilia and flagella are dynamic organelles whose assembly and maintenance depend on an activetrafficking process known as the IntraFlagellar Transport (IFT), during which trains of IFT protein particles are moved by specific motors and carry flagellar precursors and turnover products along the axoneme. IFT consists of an anterograde (from base to tip) and a retrograde (from tip to base) phase. During IFT turnaround at the flagellar tip, anterograde trains release their cargoes and remodel to form the retrograde trains. Thus, turnaround is crucial for correct IFT. However, current knowledge of its mechanisms is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We show here that in Chlamydomonas flagella the distal ∼200 nm central pair (CP) segment is structurally differentiated for the presence of a ladder-like structure (LLS). During IFT turnaround, the IFT172 subunit dissociates from the IFT- B protein complex and binds to the LLS-containing CP segment, while the IFT-B complex participates in the assembly of the CP capping structures. The IFT scaffolding function played by the LLS-containing CP segment relies on anchoring components other than the CP microtubules, since IFT turnaround occurs also in the CP-devoid pf18 mutant flagella.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>During IFT turnaround in Chlamydomonas flagella, i) the LLS and the CP terminal plates act as anchoring platforms for IFT172 and the IFT-B complex, respectively, and ii) during its remodeling, the IFT-B complex contributes to the assembly of the CP capping structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Our results indicate that in full length Chlamydomonas flagella IFT remodeling occurs by a specialized mechanism that involves flagellar tip structures and is distinct from the previously proposed model in which the capability to reverse motility would be intrinsic of IFT train and independent by any other flagellar structure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 12","pages":"349-364"},"PeriodicalIF":2.7,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40356059","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":"Hepatitis B virus movement through the hepatocyte: An update","authors":"Reinhild Prange","doi":"10.1111/boc.202200060","DOIUrl":"10.1111/boc.202200060","url":null,"abstract":"<p>Viruses are obligate intracellular pathogens that utilize cellular machinery for many aspects of their propagation and effective egress of virus particles from host cells is one important determinant of virus infectivity. Hijacking host cell processes applies in particular to the hepatitis B virus (HBV), as its DNA genome with about 3 kb in size is one of the smallest viral genomes known. HBV is a leading cause of liver disease and still displays one of the most successful pathogens in human populations worldwide. The extremely successful spread of this virus is explained by its efficient transmission strategies and its versatile particle types, including virions, empty envelopes, naked capsids, and others. HBV exploits distinct host trafficking machineries to assemble and release its particle types including nucleocytoplasmic shuttling transport, secretory, and exocytic pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Understanding how HBV uses and subverts host membrane trafficking systems offers the chance of obtaining new mechanistic insights into the regulation and function of this essential cellular processes. It can also help to identify potential targets for antiviral interventions. Here, I will provide an overview of HBV maturation, assembly, and budding, with a focus on recent advances, and will point out areas where questions remain that can benefit from future studies. Unless otherwise indicated, almost all presented knowledge was gained from cell culture-based, HBV in vitro-replication and in vitro-infection systems.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 12","pages":"325-348"},"PeriodicalIF":2.7,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40623297","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":"CMT2A-linked mitochondrial hyperfusion-driving mutant MFN2 perturbs ER-mitochondrial associations and Ca2+ homeostasis","authors":"Rajdeep Das, Subhrangshu Das, Saikat Chakrabarti, Oishee Chakrabarti","doi":"10.1111/boc.202100098","DOIUrl":"https://doi.org/10.1111/boc.202100098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Mitofusin2 (MFN2), an important molecular player that regulates mitochondrial fusion, also helps maintain the inter-organellar contact sites, referred as mitochondria associated membranes (MAMs) that exist between the ER and mitochondria. The study deals with a mutant of MFN2, R364W-MFN2, linked with the neuropathy, Charcot Marie Tooth (CMT) disease. Previous studies show that this mutant promotes mitochondrial hyperfusion. Here, we try to decipher the role of R364W-MFN2 in affecting the ER mitochondrial associations at the MAM junctions and inter-organellar calcium signalling between the ER and the mitochondria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results show that R364W-MFN2 altered ER-mitochondria association at the MAM junctions, predisposed mitochondria towards cellular stress with the mitochondria undergoing rapid fission upon induction of mild stress and perturbs inter-organellar calcium homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results indicate that R364W-MFN2 not only affects mitochondrial morphology and dynamics but also modulate its interaction with the ER and Ca<sup>2+</sup> signalling between the two organelles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study provides significant insight that presence of the R364W-MFN2 mutation makes cells susceptible towards stress, thus negatively affecting cellular health which altogether might culminate in the form of the CMT neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 11","pages":"309-319"},"PeriodicalIF":2.7,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72304421","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":"Issue Information","authors":"","doi":"10.1002/tax.12530","DOIUrl":"https://doi.org/10.1002/tax.12530","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43303138","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":"Adenovirus receptors on antigen-presenting cells of the skin","authors":"Elina Gerber-Tichet Dienst, Eric J. Kremer","doi":"10.1111/boc.202200043","DOIUrl":"10.1111/boc.202200043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Skin, the largest human organ, is part of the first line of physical and immunological defense against many pathogens. Understanding how skin antigen-presenting cells (APCs) respond to viruses or virus-based vaccines is crucial to develop antiviral pharmaceutics, and efficient and safe vaccines. Here, we discuss the way resident and recruited skin APCs engage adenoviruses and the impact on innate immune responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 11","pages":"297-308"},"PeriodicalIF":2.7,"publicationDate":"2022-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40650486","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}
Jesús S. Distel, Rodolfo M. Ortiz Flores, Arthur Bienvenu, Milton O. Aguilera, Matteo Bonazzi, Walter Berón
{"title":"Ezrin and CD44 participate in the internalization process of Coxiella burnetii into non-phagocytic cells","authors":"Jesús S. Distel, Rodolfo M. Ortiz Flores, Arthur Bienvenu, Milton O. Aguilera, Matteo Bonazzi, Walter Berón","doi":"10.1111/boc.202100096","DOIUrl":"10.1111/boc.202100096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Ezrin protein is involved in the interaction of actin cytoskeleton with membrane receptors such as CD44. It regulates plasma membrane dynamics and intracellular signaling. <i>Coxiella burnetii</i>, the etiologic agent of Q fever, is internalized into host cell through a poorly characterized molecular mechanism. Here we analyzed the role of ezrin and CD44 in the <i>C. burnetii</i> internalization by HeLa cells. The knockdown of ezrin and CD44 inhibited the bacterial uptake. Interestingly, at early stages of <i>C. burnetii</i> internalization, ezrin was recruited to the cell membrane fraction and phosphorylated. Moreover, the overexpression of non-phosphorylatable and phosphomimetic ezrin mutants decreased and increased the bacterial entry, respectively. A decrease in the internalization of <i>C. burnetii</i> was observed by the overexpression of CD44 truncated forms containing the intracellular or the extracellular domains. Interestingly, the CD44 mutant was unable to interact with ERM proteins decreased the bacterial internalization. These findings demonstrate the participation of ezrin in the internalization process of <i>C. burnetii</i> in non-phagocytic cells. Additionally, we present evidence that CD44 receptor would be involved in that process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"114 9","pages":"237-253"},"PeriodicalIF":2.7,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40605888","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}
Aurore de Poret, Rayane Dibsy, Peggy Merida, Alice Trausch, Kaushik Inamdar, Delphine Muriaux
{"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, Rayane Dibsy, Peggy Merida, Alice Trausch, Kaushik Inamdar, 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}
Sushila Kumari, Prasanta K. Dash, Tripti Kumari, Ming-Lei Guo, Jimut Kanti Ghosh, Shilpa J. Buch, Raj Kamal Tripathi
{"title":"HIV-1 Nef hijacks both exocytic and endocytic pathways of host intracellular trafficking through differential regulation of Rab GTPases","authors":"Sushila Kumari, Prasanta K. Dash, Tripti Kumari, Ming-Lei Guo, Jimut Kanti Ghosh, Shilpa J. Buch, 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<sub>NL4-3</sub> 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}
Rieko Tanaka-Yachi, Kazuko Aizawa, Kie shimizu, Hidenori Akutsu, Kazuaki Nakamura
{"title":"Low-density cell culture enhances hepatic function through tight junction formation in HepG2 cells","authors":"Rieko Tanaka-Yachi, Kazuko Aizawa, Kie shimizu, Hidenori Akutsu, 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}