European journal of cell biology最新文献

{"title":"Thrombospondin 4, a mediator and candidate indicator of pain","authors":"Yanqiong Wu ,&nbsp;Min Yang ,&nbsp;Xueqin Xu ,&nbsp;Yan Gao ,&nbsp;Xiaohui Li ,&nbsp;Yang Li ,&nbsp;Shanchun Su ,&nbsp;Xianqiao Xie ,&nbsp;Zeyong Yang ,&nbsp;Changbin Ke","doi":"10.1016/j.ejcb.2024.151395","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151395","url":null,"abstract":"<div><p>Pain is the most common symptom for which patients seek medical attention. Existing treatments for pain control are largely ineffective due to the lack of an accurate way to objectively measure pain intensity and a poor understanding of the etiology of pain. Thrombospondin 4(TSP4), a member of the thrombospondin gene family, is expressed in neurons and astrocytes and induces pain by interacting with the calcium channel alpha-2-delta-1 subunit (Cavα2δ1). In the present study we show that TSP4 expression level correlates positively with pain intensity, suggesting that TSP4 could be a novel candidate of pain indicator. Using RNAi-lentivirus (RNAi-LV) to knock down TSP4 both in vivo and in vitro, together with electrophysiological experiments involving paired patch-clamp recordings of evoked action potentials and post-synaptic currents in cultured neurons, we found that TSP4 contributes to the development of bone cancer pain, neuropathic pain, and inflammatory pain. This effect is mediated by regulation of neuron excitability via inhibition of synapsin I (Syn I) and modulation of excitatory and inhibitory presynaptic transmission via regulation of vesicular glutamate transporter 2(Vglut2), vesicular GABA transporter (VGAT), and glutamate decarboxylase (GAD) expression. The present study provides a replicable, predictive, valid indicator of pain and demonstrated the underlying molecular and electrophysiological mechanisms by which TSP4 contributes to pain.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151395"},"PeriodicalIF":6.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000128/pdfft?md5=b8aeb088b41612bf9e0db1b3f579b49c&pid=1-s2.0-S0171933524000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The nexus of nuclear envelope dynamics, circular economy and cancer cell pathophysiology","authors":"Kristina Keuper ,&nbsp;Jiri Bartek ,&nbsp;Apolinar Maya-Mendoza","doi":"10.1016/j.ejcb.2024.151394","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151394","url":null,"abstract":"<div><p>The nuclear envelope (NE) is a critical component in maintaining the function and structure of the eukaryotic nucleus. The NE and lamina are disassembled during each cell cycle to enable an open mitosis. Nuclear architecture construction and deconstruction is a prime example of a circular economy, as it fulfills a highly efficient recycling program bound to continuous assessment of the quality and functionality of the building blocks. Alterations in the nuclear dynamics and lamina structure have emerged as important contributors to both oncogenic transformation and cancer progression. However, the knowledge of the NE breakdown and reassembly is still limited to a fraction of participating proteins and complexes. As cancer cells contain highly diverse nuclei in terms of DNA content, but also in terms of nuclear number, size, and shape, it is of great interest to understand the intricate relationship between these nuclear features in cancer cell pathophysiology. In this review, we provide insights into how those NE dynamics are regulated, and how lamina destabilization processes may alter the NE circular economy. Moreover, we expand the knowledge of the lamina-associated domain region by using strategic algorithms, including Artificial Intelligence, to infer protein associations, assess their function and location, and predict cancer-type specificity with implications for the future of cancer diagnosis, prognosis and treatment. Using this approach we identified NUP98 and MECP2 as potential proteins that exhibit upregulation in Acute Myeloid Leukemia (LAML) patients with implications for early diagnosis.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151394"},"PeriodicalIF":6.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000116/pdfft?md5=5df94848a0f1ae093e002cd976953089&pid=1-s2.0-S0171933524000116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High throughput methods to study protein-protein interactions during host-pathogen interactions","authors":"Giridhar Chandrasekharan,&nbsp;Meera Unnikrishnan","doi":"10.1016/j.ejcb.2024.151393","DOIUrl":"10.1016/j.ejcb.2024.151393","url":null,"abstract":"<div><p>The ability of a pathogen to survive and cause an infection is often determined by specific interactions between the host and pathogen proteins. Such interactions can be both intra- and extracellular and may define the outcome of an infection. There are a range of innovative biochemical, biophysical and bioinformatic techniques currently available to identify protein-protein interactions (PPI) between the host and the pathogen. However, the complexity and the diversity of host-pathogen PPIs has led to the development of several high throughput (HT) techniques that enable the study of multiple interactions at once and/or screen multiple samples at the same time, in an unbiased manner. We review here the major HT laboratory-based technologies employed for host-bacterial interaction studies.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151393"},"PeriodicalIF":6.6,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000104/pdfft?md5=d41c542036c55accba7ce0a2aa219c79&pid=1-s2.0-S0171933524000104-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139554242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the HIF switch in human endothelial and cancer cells","authors":"Jakub Slawski ,&nbsp;Maciej Jaśkiewicz ,&nbsp;Anna Barton ,&nbsp;Sylwia Kozioł ,&nbsp;James F. Collawn ,&nbsp;Rafał Bartoszewski","doi":"10.1016/j.ejcb.2024.151386","DOIUrl":"10.1016/j.ejcb.2024.151386","url":null,"abstract":"<div><p>Hypoxia-inducible factors (HIFs) are transcription factors that reprogram the transcriptome for cells to survive hypoxic insults and oxidative stress. They are important during embryonic development and reprogram the cells to utilize glycolysis when the oxygen levels are extremely low. This metabolic change facilitates normal cell survival as well as cancer cell survival. The key feature in survival is the transition between acute hypoxia and chronic hypoxia, and this is regulated by the transition between HIF-1 expression and HIF-2/HIF-3 expression. This transition is observed in many human cancers and endothelial cells and referred to as the HIF Switch. Here we discuss the mechanisms involved in the HIF Switch in human endothelial and cancer cells which include mRNA and protein levels of the alpha chains of the HIFs. A major continuing effort in this field is directed towards determining the differences between normal and tumor cell utilization of this important pathway, and how this could lead to potential therapeutic approaches.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151386"},"PeriodicalIF":6.6,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000037/pdfft?md5=2ee1e8079d88c9d595cd79d7303ffadd&pid=1-s2.0-S0171933524000037-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Ozone mediates the anticancer effect of air plasma by triggering oxidative cell death caused by H2O2 and iron” [Eur. J. Cell Biol. 102 (2023) 151346]","authors":"M. Suzuki-Karasaki ,&nbsp;Y. Ochiai ,&nbsp;S. Innami ,&nbsp;H. Okajima ,&nbsp;H. Nakayama ,&nbsp;Y. Suzuki-Karasaki","doi":"10.1016/j.ejcb.2024.151385","DOIUrl":"10.1016/j.ejcb.2024.151385","url":null,"abstract":"","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151385"},"PeriodicalIF":6.6,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000025/pdfft?md5=e4d9168fbce927d97576828cdb21e0a3&pid=1-s2.0-S0171933524000025-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139476962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helical motors and formins synergize to compact chiral filopodial bundles: A theoretical perspective","authors":"Ondrej Maxian ,&nbsp;Alex Mogilner","doi":"10.1016/j.ejcb.2023.151383","DOIUrl":"https://doi.org/10.1016/j.ejcb.2023.151383","url":null,"abstract":"<div><p>Chiral actin bundles have been shown to play an important role in cell dynamics, but our understanding of the molecular mechanisms which combine to generate chirality remains incomplete. To address this, we numerically simulate a crosslinked filopodial bundle under the actions of helical myosin motors and/or formins and examine the collective buckling and twisting of the actin bundle. We first show that a number of proposed mechanisms to buckle polymerizing actin bundles without motor activity fail under biologically-realistic parameters. We then demonstrate that a simplified model of myosin spinning action at the bundle base effectively “braids” the bundle, but cannot control compaction at the fiber tips. Finally, we show that formin-mediated polymerization and motor activity can act synergitically to compact filopodium bundles, as motor activity bends filaments into shapes that activate twist forces induced by formins. Stochastic fluctuations of actin polymerization rates and slower cross linking dynamics both increase buckling and decrease compaction. We discuss implications of our findings for mechanisms of cytoskeletal chirality.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151383"},"PeriodicalIF":6.6,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000985/pdfft?md5=c6e9f07a22795ec5d10968433a17a4f3&pid=1-s2.0-S0171933523000985-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139488024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controling the cytoskeleton during CEACAM3-mediated phagocytosis","authors":"Johannes W.P. Kuiper ,&nbsp;Helena L. Gregg ,&nbsp;Meike Schüber ,&nbsp;Jule Klein ,&nbsp;Christof R. Hauck","doi":"10.1016/j.ejcb.2024.151384","DOIUrl":"10.1016/j.ejcb.2024.151384","url":null,"abstract":"<div><p>Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the fastest evolving human proteins implying a special role in human biology. This receptor, CEACAM3, is a member of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule (CEACAM) family and dedicated to the immediate recognition and rapid internalization of human-restricted pathogens. In this focused contribution, we will review the special adaptations of this protein, which co-evolves with different species of mucosa-colonizing bacteria. While the extracellular Immunoglobulin-variable (Ig_V)-like domain recognizes various bacterial adhesins, an Immunoreceptor Tyrosine-based Activation Motif (ITAM)-like sequence in the cytoplasmic tail of CEACAM3 constitutes the central signaling hub to trigger actin rearrangements needed for efficient phagocytosis. A major emphasis of this review will be placed on recent findings, which have revealed the multi-level control of this powerful phagocytic device. As tyrosine phosphorylation and small GTPase activity are central for CEACAM3-mediated phagocytosis, the counterregulation of CEACAM3 activity involves the receptor-type protein tyrosine phosphatase J (PTPRJ) as well as the Rac-GTP scavenging protein Cyri-B. Interference with such negative regulatory circuits has revealed that CEACAM3-mediated phagocytosis can be strongly enhanced. In principle, the knowledge gained by studying CEACAM3 can be applied to other phagocytic systems and opens the door to treatments, which boost the phagocytic capacity of professional phagocytes.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151384"},"PeriodicalIF":6.6,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000013/pdfft?md5=4798bb4d47d6bfa948d88ff0b3ae6059&pid=1-s2.0-S0171933524000013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shigella generates distinct IAM subpopulations during epithelial cell invasion to promote efficient intracellular niche formation","authors":"Lisa Sanchez ,&nbsp;Arthur Lensen ,&nbsp;Michael G. Connor ,&nbsp;Mélanie Hamon ,&nbsp;Jost Enninga ,&nbsp;Camila Valenzuela","doi":"10.1016/j.ejcb.2023.151381","DOIUrl":"10.1016/j.ejcb.2023.151381","url":null,"abstract":"<div><p>The facultative intracellular pathogen <em>Shigella flexneri</em> invades non-phagocytic epithelial gut cells. Through a syringe-like apparatus called type 3 secretion system, it injects effector proteins into the host cell triggering actin rearrangements leading to its uptake within a tight vacuole, termed the bacterial-containing vacuole (BCV). Simultaneously, <em>Shigella</em> induces the formation of large vesicles around the entry site, which we refer to as infection-associated macropinosomes (IAMs). After entry, <em>Shigella</em> ruptures the BCV and escapes into the host cytosol by disassembling the BCV remnants. Previously, IAM formation has been shown to be required for efficient BCV escape, but the molecular events associated with BCV disassembly have remained unclear. To identify host components required for BCV disassembly, we performed a microscopy-based screen to monitor the recruitment of BAR domain-containing proteins, which are a family of host proteins involved in membrane shaping and sensing (e.g. endocytosis and recycling) during <em>Shigella</em> epithelial cell invasion. We identified endosomal recycling BAR protein Sorting Nexin-8 (SNX8) localized to IAMs in a PI(3)P-dependent manner before BCV disassembly. At least two distinct IAM subpopulations around the BCV were found, either being recycled back to cellular compartments such as the plasma membrane or transitioning to become RAB11A positive “contact-IAMs” involved in promoting BCV rupture. The IAM subpopulation duality was marked by the exclusive recruitment of either SNX8 or RAB11A. Hindering PI(3)P production at the IAMs led to an inhibition of SNX8 recruitment at these compartments and delayed both, the step of BCV rupture time and successful BCV disassembly. Finally, siRNA depletion of SNX8 accelerated BCV rupture and unpeeling of BCV remnants, indicating that SNX8 is involved in controlling the timing of the cytosolic release. Overall, our work sheds light on how <em>Shigella</em> establishes its intracellular niche through the subversion of a specific set of IAMs.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151381"},"PeriodicalIF":6.6,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000961/pdfft?md5=3bd11973c689e0755f7c6ea0e1d059a5&pid=1-s2.0-S0171933523000961-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139065539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 dynamic duo: Understanding the roles of FtsZ and FtsA for Escherichia coli cell division through in vitro approaches","authors":"Philipp Radler ,&nbsp;Martin Loose","doi":"10.1016/j.ejcb.2023.151380","DOIUrl":"10.1016/j.ejcb.2023.151380","url":null,"abstract":"<div><p>Bacteria divide by binary fission. The protein machine responsible for this process is the divisome, a transient assembly of more than 30 proteins in and on the surface of the cytoplasmic membrane. Together, they constrict the cell envelope and remodel the peptidoglycan layer to eventually split the cell into two. For <em>Escherichia coli,</em> most molecular players involved in this process have probably been identified, but obtaining the quantitative information needed for a mechanistic understanding can often not be achieved from experiments in vivo alone. Since the discovery of the Z-ring more than 30 years ago, in vitro reconstitution experiments have been crucial to shed light on molecular processes normally hidden in the complex environment of the living cell. In this review, we summarize how rebuilding the divisome from purified components – or at least parts of it - have been instrumental to obtain the detailed mechanistic understanding of the bacterial cell division machinery that we have today.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151380"},"PeriodicalIF":6.6,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017193352300095X/pdfft?md5=ce1b540279007cf70ec91310a99842f6&pid=1-s2.0-S017193352300095X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139056575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes","authors":"Dante Barreda ,&nbsp;Sergio Grinstein ,&nbsp;Spencer A. Freeman","doi":"10.1016/j.ejcb.2023.151382","DOIUrl":"10.1016/j.ejcb.2023.151382","url":null,"abstract":"<div><p>The ongoing phagocytic activity of macrophages necessitates an extraordinary capacity to digest and resolve incoming material. While the initial steps leading to the formation of a terminal phagolysosome are well studied, much less is known about the later stages of this process, namely the degradation and resolution of the phagolysosomal contents. We report that the degradation of targets such as splenocytes and erythrocytes by phagolysosomes occurs in a stepwise fashion, requiring lysis of their plasmalemmal bilayer as an essential initial step. This is achieved by the direct extraction of cholesterol facilitated by Niemann-Pick protein type C2 (NPC2), which in turn hands off cholesterol to NPC1 for export from the phagolysosome. The removal of cholesterol ulimately destabilizes and permeabilizes the membrane of the phagocytic target, allowing access of hydrolases to its internal compartments. In contrast, we found that saposins, which activate the hydrolysis of sphingolipids, are required for lysosomal tubulation, yet are dispensable for the resolution of targets by macrophages. The extraction of cholesterol by NPC2 is therefore envisaged as rate-limiting in the clearance of membrane-bound targets such as apoptotic cells. Selective cholesterol removal appears to be a primary mechanism that enables professional phagocytes to distinguish the target membrane from the phagolysosomal membrane and may be conserved in the resolution of autolysosomes.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151382"},"PeriodicalIF":6.6,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000973/pdfft?md5=c78c7e05b9ed761063e5657746183228&pid=1-s2.0-S0171933523000973-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139056255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}