European journal of cell biology最新文献

{"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}

{"title":"Cofilin-mediated actin filament network flexibility facilitates 2D to 3D actomyosin shape change","authors":"Zachary Gao Sun ,&nbsp;Vikrant Yadav ,&nbsp;Sorosh Amiri ,&nbsp;Wenxiang Cao ,&nbsp;Enrique M. De La Cruz ,&nbsp;Michael Murrell","doi":"10.1016/j.ejcb.2023.151379","DOIUrl":"10.1016/j.ejcb.2023.151379","url":null,"abstract":"<div><p>The organization of actin filaments (F-actin) into crosslinked networks determines the transmission of mechanical stresses within the cytoskeleton and subsequent changes in cell and tissue shape. Principally mediated by proteins such as α-actinin, F-actin crosslinking increases both network connectivity and rigidity, thereby facilitating stress transmission at low crosslinking yet attenuating transmission at high crosslinker concentration. Here, we engineer a two-dimensional model of the actomyosin cytoskeleton, in which myosin-induced mechanical stresses are controlled by light. We alter the extent of F-actin crosslinking by the introduction of oligomerized cofilin. At pH 6.5, F-actin severing by cofilin is weak, but cofilin bundles and crosslinks filaments. Given its effect of lowering the F-actin bending stiffness, cofilin- crosslinked networks are significantly more flexible and softer in bending than networks crosslinked by α-actinin. Thus, upon local activation of myosin-induced contractile stress, the network bends out-of-plane in contrast to the in-plane compression as observed with networks crosslinked by α-actinin. Here, we demonstrate that local effects on filament mechanics by cofilin introduces novel large-scale network material properties that enable the sculpting of complex shapes in the cell cytoskeleton.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151379"},"PeriodicalIF":6.6,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000948/pdfft?md5=102d7dc5b962eaf97acf510530b119ac&pid=1-s2.0-S0171933523000948-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139056188","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":"Direct observation of cortactin protecting Arp2/3-actin filament branch junctions from GMF-mediated destabilization","authors":"Emma R. McGuirk ,&nbsp;Neha Koundinya ,&nbsp;Priyashree Nagarajan ,&nbsp;Shae B. Padrick ,&nbsp;Bruce L. Goode","doi":"10.1016/j.ejcb.2023.151378","DOIUrl":"10.1016/j.ejcb.2023.151378","url":null,"abstract":"<div><p>How cells tightly control the formation and turnover of branched actin filament arrays to drive cell motility, endocytosis, and other cellular processes is still not well understood. Here, we investigated the mechanistic relationship between two binding partners of the Arp2/3 complex, glia maturation factor (GMF) and cortactin. Individually, GMF and cortactin have opposite effects on the stability of actin filament branches, but it is unknown how they work in concert with each other to govern branch turnover. Using TIRF microscopy, we observe that GMF’s branch destabilizing activities are potently blocked by cortactin (IC₅₀ = 1.3 nM) and that this inhibition requires direct interactions of cortactin with Arp2/3 complex. The simplest model that would explain these results is competition for binding Arp2/3 complex. However, we find that cortactin and GMF do not compete for free Arp2/3 complex in solution. Further, we use single molecule analysis to show that cortactin’s on-rate (3 ×10⁷ s⁻¹ M⁻¹) and off-rate (0.03 s⁻¹) at branch junctions are minimally affected by excess GMF. Together, these results show that cortactin binds with high affinity to branch junctions, where it blocks the destabilizing effects of GMF, possibly by a mechanism that is allosteric in nature. In addition, the affinities we measure for cortactin at actin filament branch junctions (K_d = 0.9 nM) and filament sides (K_d = 206 nM) are approximately 20-fold stronger than previously reported. These observations contribute to an emerging view of molecular complexity in how Arp2/3 complex is regulated through the integration of multiple inputs.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151378"},"PeriodicalIF":6.6,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000936/pdfft?md5=957f52af14d82f8297182a46b1bbbdc6&pid=1-s2.0-S0171933523000936-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138540818","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":"Impact of heat and cold shock on epigenetics and chromatin structure","authors":"Claudio Casali ,&nbsp;Luca Galgano ,&nbsp;Lorena Zannino ,&nbsp;Stella Siciliani ,&nbsp;Margherita Cavallo ,&nbsp;Giuliano Mazzini ,&nbsp;Marco Biggiogera","doi":"10.1016/j.ejcb.2023.151373","DOIUrl":"https://doi.org/10.1016/j.ejcb.2023.151373","url":null,"abstract":"<div><p>Cells are continuously exposed to various sources of insults, among which temperature variations are extremely common. Epigenetic mechanisms, critical players in gene expression regulation, undergo alterations due to these stressors, potentially leading to health issues. Despite the significance of DNA methylation and histone modifications in gene expression regulation, their changes following heat and cold shock in human cells remain poorly understood. In this study, we investigated the epigenetic profiles of human cells subjected to hyperthermia and hypothermia, revealing significant variations. Heat shock primarily led to DNA methylation increments and epigenetic modifications associated with gene expression silencing. In contrast, cold shock presented a complex scenario, with both methylation and demethylation levels increasing, indicating different epigenetic responses to the opposite thermal stresses. These temperature-induced alterations in the epigenome, particularly their impact on chromatin structural organization, represent an understudied area that could offer important insights into genome function and potential prospects for therapeutic targets.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151373"},"PeriodicalIF":6.6,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000882/pdfft?md5=9f314a4aa812057f9f49d24cdd9966b4&pid=1-s2.0-S0171933523000882-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138448377","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":"Oxidative stress and signaling through EGFR and PKA pathways converge on the nuclear transport factor RanBP1","authors":"Mohamed Kodiha,&nbsp;Nabila Azad,&nbsp;Siwei Chu,&nbsp;Noah Crampton,&nbsp;Ursula Stochaj","doi":"10.1016/j.ejcb.2023.151376","DOIUrl":"https://doi.org/10.1016/j.ejcb.2023.151376","url":null,"abstract":"<div><p>Nuclear protein trafficking requires the soluble transport factor RanBP1. The subcellular distribution of RanBP1 is dynamic, as the protein shuttles between the nucleus and cytoplasm. To date, the signaling pathways regulating RanBP1 subcellular localization are poorly understood. During interphase, RanBP1 resides mostly in the cytoplasm. We show here that oxidative stress concentrates RanBP1 in the nucleus, and our study defines the underlying mechanisms. Specifically, RanBP1’s cysteine residues are not essential for its oxidant-induced relocation. Furthermore, our pharmacological approaches uncover that signaling mediated by epidermal growth factor receptor (EGFR) and protein kinase A (PKA) control RanBP1 localization during stress. In particular, pharmacological inhibitors of EGFR or PKA diminish the oxidant-dependent relocation of RanBP1. Mutant analysis identified serine 60 and tyrosine 103 as regulators of RanBP1 nuclear accumulation during oxidant exposure. Taken together, our results define RanBP1 as a target of oxidative stress and a downstream effector of EGFR and PKA signaling routes. This positions RanBP1 at the intersection of important cellular signaling circuits.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151376"},"PeriodicalIF":6.6,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000912/pdfft?md5=a5db7a8f5ebd50b171a7c4c5879ca2f7&pid=1-s2.0-S0171933523000912-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437760","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":"Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration","authors":"M.J. Nunes ,&nbsp;A.N. Carvalho ,&nbsp;C. Sá-Lemos ,&nbsp;M. Colaço ,&nbsp;I. Cervenka ,&nbsp;V. Ciraci ,&nbsp;S.G. Santos ,&nbsp;M.M. Ribeiro ,&nbsp;M. Castanheira ,&nbsp;P.R. Jannig ,&nbsp;M.J. Gama ,&nbsp;M. Castro-Caldas ,&nbsp;C.M.P. Rodrigues ,&nbsp;E. Rodrigues ,&nbsp;J.L. Ruas","doi":"10.1016/j.ejcb.2023.151377","DOIUrl":"https://doi.org/10.1016/j.ejcb.2023.151377","url":null,"abstract":"<div><p>Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and as potential therapeutic targets for the treatment of PD and other neurodegenerative disorders.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 1","pages":"Article 151377"},"PeriodicalIF":6.6,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933523000924/pdfft?md5=b5704f122c0a6eba2f271e71ab980995&pid=1-s2.0-S0171933523000924-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138396775","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}