Biology of the Cell最新文献

{"title":"Alpha-arrestins Aly1/Art6 and Aly2/Art3 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis","authors":"Benjamin P. Robinson,&nbsp;Sarah Hawbaker,&nbsp;Annette Chiang,&nbsp;Eric M. Jordahl,&nbsp;Sanket Anaokar,&nbsp;Alexiy Nikiforov,&nbsp;Ray W. Bowman II,&nbsp;Philip Ziegler,&nbsp;Ceara K. McAtee,&nbsp;Jana Patton-Vogt,&nbsp;Allyson F. O'Donnell","doi":"10.1111/boc.202100007","DOIUrl":"10.1111/boc.202100007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background information</h3>\u0000 \u0000 <p>Phosphatidylinositol (PI) is an essential phospholipid, critical to membrane bilayers. The complete deacylation of PI by B-type phospholipases produces intracellular and extracellular glycerophosphoinositol (GPI). Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters at the yeast plasma membrane. Internalized GPI is degraded to produce inositol, phosphate and glycerol, thereby contributing to these pools. <i>GIT1</i> gene expression is controlled by nutrient balance, with phosphate or inositol starvation increasing <i>GIT1</i> expression to stimulate GPI uptake. However, less is known about control of Git1 protein levels or localization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find that the α-arrestins, an important class of protein trafficking adaptor, regulate Git1 localization and this is dependent upon their interaction with the ubiquitin ligase Rsp5. Specifically, α-arrestin Aly2 stimulates Git1 trafficking to the vacuole under basal conditions, but in response to GPI-treatment, either Aly1 or Aly2 promote Git1 vacuole trafficking. Cell surface retention of Git1, as occurs in <i>aly1</i>∆ <i>aly2</i>∆ cells, is linked to impaired growth in the presence of exogenous GPI and results in increased uptake of radiolabeled GPI, suggesting that accumulation of GPI somehow causes cellular toxicity. Regulation of α-arrestin Aly1 by the protein phosphatase calcineurin improves steady-state and substrate-induced trafficking of Git1, however, calcineurin plays a larger role in Git1 trafficking beyond regulation of α-arrestins. Interestingly, loss of Aly1 and Aly2 increased phosphatidylinositol-3-phosphate on the limiting membrane of the vacuole, and this was further exacerbated by GPI addition, suggesting that the effect is partially linked to Git1. Loss of Aly1 and Aly2 leads to increased incorporation of inositol label from [³H]-inositol-labelled GPI into PI, confirming that internalized GPI influences PI balance and indicating a role for the a-arrestins in this regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The α-arrestins Aly1 and Aly2 are novel regulators of Git1 trafficking with previously unanticipated roles in controlling phospholipid distribution and balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>To our knowledge, this is the first example of α-arrestin regulation of phosphatidyliniositol-3-phosphate levels. In future studies it will be exciting to determine if other α-arrestins similarly alter PI and PIPs to change the cellular landscape.</p>\u0000 </section>\u0000 ","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202100007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39450052","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":"A new pancreatic adenocarcinoma-derived organoid model of acquired chemoresistance to FOLFIRINOX: First insight of the underlying mechanisms","authors":"Elsa Hadj Bachir,&nbsp;Charles Poiraud,&nbsp;Sonia Paget,&nbsp;Nicolas Stoup,&nbsp;Soumaya El Moghrabi,&nbsp;Belinda Duchêne,&nbsp;Nathalie Jouy,&nbsp;Antonino Bongiovanni,&nbsp;Meryem Tardivel,&nbsp;Louis-Bastien Weiswald,&nbsp;Marie Vandepeutte,&nbsp;César Beugniez,&nbsp;Fabienne Escande,&nbsp;Emmanuelle Leteurtre,&nbsp;OrgaRES consortium,&nbsp;Laurent Poulain,&nbsp;Chann Lagadec,&nbsp;Pascal Pigny,&nbsp;Nicolas Jonckheere,&nbsp;Florence Renaud,&nbsp;Stephanie Truant,&nbsp;Isabelle Van Seuningen,&nbsp;Audrey Vincent","doi":"10.1111/boc.202100003","DOIUrl":"10.1111/boc.202100003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Although improvements have been made in the management of pancreatic adenocarcinoma (PDAC) during the past 20 years, the prognosis of this deadly disease remains poor with an overall 5-year survival under 10%. Treatment with FOLFIRINOX, a combined regimen of 5-fluorouracil, irinotecan (SN-38) and oxaliplatin, is nonetheless associated with an excellent initial tumour response and its use has allowed numerous patients to go through surgery while their tumour was initially considered unresectable. These discrepancies between initial tumour response and very low long-term survival are the consequences of rapidly acquired chemoresistance and represent a major therapeutic frontier. To our knowledge, a model of resistance to the combined three drugs has never been described due to the difficulty of modelling the FOLFIRINOX protocol both in vitro and in vivo. Patient-derived tumour organoids (PDO) are the missing link that has long been lacking in the wide range of epithelial cancer models between 2D adherent cultures and in vivo xenografts. In this work we sought to set up a model of PDO with resistance to FOLFIRINOX regimen that we could compare to the paired naive PDO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first extrapolated physiological concentrations of the three drugs using previous pharmacodynamics studies and bi-compartmental elimination models of oxaliplatin and SN-38. We then treated PaTa-1818x naive PDAC organoids with six cycles of 72 h-FOLFIRINOX treatment followed by 96 h interruption. Thereafter, we systematically compared treated organoids to PaTa-1818x naive organoids in terms of growth, proliferation, viability and expression of genes involved in cancer stemness and aggressiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We reproductively obtained resistant organoids FoxR that significantly showed less sensitivity to FOLFORINOX treatment than the PaTa-1818x naive organoids from which they were derived. Our resistant model is representative of the sequential steps of chemoresistance observed in patients in terms of growth arrest (proliferation blockade), residual disease (cell quiescence/dormancy) and relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>To our knowledge, this is the first genuine in vitro model of resistance to the three drugs in combined therapy. This new PDO model will be a great asset for the discovery of acquired chemoresistance mechanisms, knowledge that is mandatory before offering new therapeutic strategies for pancreatic cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202100003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39447323","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":"Decreased proliferation of aged rat beta cells corresponds with enhanced expression of the cell cycle inhibitor p27KIP1","authors":"Talon J. Aitken,&nbsp;Jacqueline E. Crabtree,&nbsp;Daelin M. Jensen,&nbsp;Kavan H. Hess,&nbsp;Brennan R. Leininger,&nbsp;Jeffery S. Tessem","doi":"10.1111/boc.202100035","DOIUrl":"10.1111/boc.202100035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Over 400 million people are diabetic. Type 1 and type 2 diabetes are characterized by decreased functional β-cell mass and, consequently, decreased glucose-stimulated insulin secretion. A potential intervention is transplantation of β-cell containing islets from cadaveric donors. A major impediment to greater application of this treatment is the scarcity of transplant-ready β-cells. Therefore, inducing β-cell proliferation ex vivo could be used to expand functional β-cell mass prior to transplantation. Various molecular pathways are sufficient to induce proliferation of young β-cells; however, aged β-cells are refractory to these proliferative signals. Given that the majority of cadaveric donors fit an aged demographic, defining the mechanisms that impede aged β-cell proliferation is imperative.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that aged rat (5-month-old) β-cells are refractory to mitogenic stimuli that otherwise induce young rat (5-week-old) β-cell proliferation. We hypothesized that this change in proliferative capacity could be due to differences in cyclin-dependent kinase inhibitor expression. We measured levels of p16^INK4a, p15^INK4b, p18^INK4c, p19^INK4d, p21^CIP1, p27^KIP1 and p57^KIP2 by immunofluorescence analysis. Our data demonstrates an age-dependent increase of p27^KIP1 in rat β-cells by immunofluorescence and was validated by increased p27^KIP1 protein levels by western blot analysis. Interestingly, HDAC1, which modulates the p27^KIP1 promoter acetylation state, is downregulated in aged rat islets. These data demonstrate increased p27^KIP1 protein levels at 5 months of age, which may be due to decreased HDAC1 mediated repression of p27^KIP1 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>As the majority of transplant-ready β-cells come from aged donors, it is imperative that we understand why aged β-cells are refractory to mitogenic stimuli. Our findings demonstrate that increased p27^KIP1 expression occurs early in β-cell aging, which corresponds with impaired β-cell proliferation. Furthermore, the correlation between HDAC1 and p27 levels suggests that pathways that activate HDAC1 in aged β-cells could be leveraged to decrease p27^KIP1 levels and enhance β-cell proliferation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202100035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39436553","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":"Role of regulatory C-terminal motifs in synaptic confinement of LRRTM2","authors":"Konstantina Liouta,&nbsp;Julia Chabbert,&nbsp;Sebastien Benquet,&nbsp;Béatrice Tessier,&nbsp;Vincent Studer,&nbsp;Matthieu Sainlos,&nbsp;Joris De Wit,&nbsp;Olivier Thoumine,&nbsp;Ingrid Chamma","doi":"10.1111/boc.202100026","DOIUrl":"10.1111/boc.202100026","url":null,"abstract":"<p>Leucine Rich Repeat Transmembrane proteins (LRRTMs) are neuronal cell adhesion molecules involved in synapse development and plasticity. LRRTM2 is the most synaptogenic isoform of the family, and its expression is strongly restricted to excitatory synapses in mature neurons. However, the mechanisms by which LRRTM2 is trafficked and stabilized at synapses remain unknown. Here, we examine the role of LRRTM2 intracellular domain on its membrane expression and stabilization at excitatory synapses, using a knock-down strategy combined to single molecule tracking and super-resolution dSTORM microscopy. We show that LRRTM2 operates an important shift in mobility after synaptogenesis in hippocampal neurons. Knock-down of LRRTM2 during synapse formation reduced excitatory synapse density in mature neurons. Deletion of LRRTM2 C-terminal domain abolished the compartmentalization of LRRTM2 in dendrites and disrupted its synaptic enrichment. Furtheremore, we show that LRRTM2 diffusion is increased in the absence of its intracellular domain, and that the protein is more dispersed at synapses. Surprisingly, LRRTM2 confinement at synapses was strongly dependent on a YxxC motif in the C-terminal domain, but was independent of the PDZ-like binding motif ECEV. Finally, the nanoscale organization of LRRTM2 at excitatory synapses depended on its C-terminal domain, with involvement of both the PDZ-binding and YxxC motifs. Altogether, these results demonstrate that LRRTM2 trafficking and enrichment at excitatory synapses are dependent on its intracellular domain.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202100026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39415695","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":"Quantitative dSTORM super-resolution microscopy localizes Aurora kinase A/AURKA in the mitochondrial matrix","authors":"Béatrice Durel,&nbsp;Charles Kervrann,&nbsp;Giulia Bertolin","doi":"10.1111/boc.202100021","DOIUrl":"10.1111/boc.202100021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background information</h3>\u0000 \u0000 <p>Mitochondria are dynamic organelles playing essential metabolic and signaling functions in cells. Their ultrastructure has largely been investigated with electron microscopy (EM) techniques. However, quantifying protein-protein proximities using EM is extremely challenging. Super-resolution microscopy techniques as direct stochastic optical reconstruction microscopy (dSTORM) now provide a fluorescent-based, quantitative alternative to EM. Recently, super-resolution microscopy approaches including dSTORM led to valuable advances in our knowledge of mitochondrial ultrastructure, and in linking it with new insights in organelle functions. Nevertheless, dSTORM is mostly used to image integral mitochondrial proteins, and there is little or no information on proteins transiently present at this compartment. The cancer-related Aurora kinase A/AURKA is a protein localized at various subcellular locations, including mitochondria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first demonstrate that dSTORM coupled to GcoPS can resolve protein proximities within individual submitochondrial compartments. Then, we show that dSTORM provides sufficient spatial resolution to visualize and quantify the most abundant pool of endogenous AURKA in the mitochondrial matrix, as previously shown for overexpressed AURKA. In addition, we uncover a smaller pool of AURKA localized at the OMM, which could have a potential functional readout. We conclude by demonstrating that aldehyde-based fixatives are more specific for the OMM pool of the kinase instead.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate that dSTORM coupled to GcoPS colocalization analysis is a suitable approach to explore the compartmentalization of non-integral mitochondrial proteins as AURKA, in a qualitative and quantitative manner. This method also opens up the possibility of analyzing the proximity between AURKA and its multiple mitochondrial partners with exquisite spatial resolution, thereby allowing novel insights into the mitochondrial functions controlled by AURKA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Probing and quantifying the presence of endogenous AURKA – a cell cycle-related protein localized at mitochondria – in the different organelle subcompartments, using quantitative dSTORM super-resolution microscopy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202100021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39370727","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":"Apoptosis induction by the stem cell factor LIN28A","authors":"Yael Attali-Padael,&nbsp;Leah Armon,&nbsp;Achia Urbach","doi":"10.1111/boc.202100011","DOIUrl":"10.1111/boc.202100011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background information</h3>\u0000 \u0000 <p>Lin28A and its paralog Lin28B are RNA binding proteins expressed in stem and progenitor cells, regulating the balance between their proliferation and differentiation. <i>In-vivo</i> and <i>in-vitro</i> experiments have shown that overexpression of these genes leads to abnormal cell proliferation, which results in many cases in cell transformation and tumor formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here we show, for the first time, that Lin28A overexpression can also lead to the opposite effect, i.e. apoptosis induction. We further demonstrate that this effect is specific to Lin28A but not to Lin28B and that it is mediated via the Let-7 independent pathway in a complex mechanism that involves at least several proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Significance</h3>\u0000 \u0000 <p>This unexpected observation suggests that cell fate regulation by Lin28 is dependent on a specific cellular/genetic context. Unraveling the cellular and molecular mechanisms underlying this Lin28A overexpression effect may pave the way for novel tumor therapeutic strategies, as Lin28 is commonly expressed in many types of tumors but not in most normal adult cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39347610","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":"10.1111/boc.202170012","DOIUrl":"https://doi.org/10.1111/boc.202170012","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202170012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42865486","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 NANOTUMOR consortium - Towards the Tumor Cell Atlas.","authors":"Florent Colin,&nbsp;Kristine Schauer,&nbsp;Ali Hamiche,&nbsp;Pierre Martineau,&nbsp;Jean-Paul Borg,&nbsp;Jan Bednar,&nbsp;Giulia Bertolin,&nbsp;Luc Camoin,&nbsp;Yves Collette,&nbsp;Stephan Dimitrov,&nbsp;Isabelle Fournier,&nbsp;Vincent Hyenne,&nbsp;Marco A Mendoza-Parra,&nbsp;Xavier Morelli,&nbsp;Philippe Rondé,&nbsp;Izabela Sumara,&nbsp;Marc Tramier,&nbsp;Patrick Schultz,&nbsp;Jacky G Goetz","doi":"10.1111/boc.202000135","DOIUrl":"https://doi.org/10.1111/boc.202000135","url":null,"abstract":"<p><p>Cancer is a multi-step disease where an initial tumour progresses through critical steps shaping, in most cases, life-threatening secondary foci called metastases. The oncogenic cascade involves genetic, epigenetic, signalling pathways, intracellular trafficking and/or metabolic alterations within cancer cells. In addition, pre-malignant and malignant cells orchestrate complex and dynamic interactions with non-malignant cells and acellular matricial components or secreted factors within the tumour microenvironment that is instrumental in the progression of the disease. As our aptitude to effectively treat cancer mostly depends on our ability to decipher, properly diagnose and impede cancer progression and metastasis formation, full characterisation of molecular complexes and cellular processes at play along the metastasis cascade is crucial. For many years, the scientific community lacked adapted imaging and molecular technologies to accurately dissect, at the highest resolution possible, tumour and stromal cells behaviour within their natural microenvironment. In that context, the NANOTUMOR consortium is a French national multi-disciplinary workforce which aims at a providing a multi-scale characterisation of the oncogenic cascade, from the atomic level to the dynamic organisation of the cell in response to genetic mutations, environmental changes or epigenetic modifications. Ultimately, this program aims at identifying new therapeutic targets using innovative drug design.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202000135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25343008","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":"Intracellular host cell membrane remodelling induced by SARS-CoV-2 infection in vitro.","authors":"Lucio Ayres Caldas,&nbsp;Fabiana Avila Carneiro,&nbsp;Fabio Luis Monteiro,&nbsp;Ingrid Augusto,&nbsp;Luiza Mendonça Higa,&nbsp;Kildare Miranda,&nbsp;Amilcar Tanuri,&nbsp;Wanderley de Souza","doi":"10.1111/boc.202000146","DOIUrl":"https://doi.org/10.1111/boc.202000146","url":null,"abstract":"<p><strong>Background information: </strong>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces an alteration in the endomembrane system of the mammalian cells. In this study, we used transmission electron microscopy and electron tomography to investigate the main structural alterations in the cytoplasm of Vero cells infected with a SARS-CoV-2 isolate from São Paulo state (Brazil).</p><p><strong>Results: </strong>Different membranous structures derived from the zippered endoplasmic reticulum were observed along with virus assembly through membrane budding. Also, we demonstrated the occurrence of annulate lamellae in the cytoplasm of infected cells and the presence of virus particles in the perinuclear space.</p><p><strong>Conclusions and significance: </strong>This study contributes to a better understanding of the cell biology of SARS-CoV-2 and the mechanisms of the interaction of the virus with the host cell that promote morphological changes, recruitment of organelles and cell components, in a context of a virus-induced membrane remodelling.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202000146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25379947","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":"Editorial.","authors":"Julien Husson","doi":"10.1111/boc.202100028","DOIUrl":"https://doi.org/10.1111/boc.202100028","url":null,"abstract":"Mechanobiology is an emerging field at the crossroads between biology, physics, mechanics, bioengineering and materials science. It investigates how mechanics can influence cell function: how cells sense and respond to external mechanical properties and forces, and how they generate forces and adapt their mechanical properties to perform functions as varied as adhesion, migration, differentiation or immune response, to name a few. A growing interest for this field is establishing a corpus of evidence suggesting that potentially any cell, of any type, can sense mechanical inputs from its environment and adapt to them. A new horizon opens up for a more comprehensive description of biological processes that includes their mechanical component. Furthermore, because external mechanical cues are involved in many pathological contexts, understanding the interplay between mechanical inputs and cell response should bring new insights into many pathologies, including cancer, atherosclerosis or evasion from immune response. This themed issue on mechanobiology covers a variety of topics at the cellular and subcellular scale. Three contributions focus on immune cells. Since pioneering studies on the biophysics of leukocytes done decades ago, a growing corpus of knowledge has been accumulated on some myeloid cells such as neutrophils. However, surprising discoveries about these foot soldiers of innate immunity are yet to come, including the way they move to explore their environment. In this issue, Garcia-Seyda et al. (2021) lead the way by showing that neutrophils can swim to reach and phagocyte their target. Mechanics of myeloid cells other than neutrophils remain to be fully explored, and Bashant et al. (2020) review how mechanical properties of myeloid cells can be quantified using recently developed high-throughput deformability cytometry. The authors review how these mechanical properties can be influenced by several factors including: differentiation, priming by cytokines and other soluble molecules or mechanical stimulation, disease and pharmacological treatment. On another front of immunobiophysics, T cells attract a lot of attention given their central role in adaptive immunity and recent revolutions in cancer immunotherapy. T cells use a complex recognition machinery to identify presented antigens. This recognition is known to be mechanosensitive, but understanding the details of this process remains the focus of active work. Before forming a synapse, T cells need to arrest on an antigen-presenting cell (APC), which is yet another process where mechanics play a role. Chabaud et al. (2020) review how mechanical forces generated at the T cell–APC interface and beard by specific bonds between T cell receptors and antigens, and adhesive bonds, regulate the arrest of T cells. This themed issue goes also subcellular with the contribution of Allard et al. (2021), which describes how the shape of membrane tubules can be remodelled by the actin cytoskeleton.","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/boc.202100028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38973483","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}