European journal of cell biology最新文献

{"title":"The expression profiles of piRNAs and their interacting Piwi proteins in cellular model of renal development: Focus on Piwil1 in mitosis","authors":"Marek Kazimierczyk,&nbsp;Agnieszka Fedoruk-Wyszomirska,&nbsp;Dorota Gurda-Woźna,&nbsp;Eliza Wyszko,&nbsp;Agata Swiatkowska,&nbsp;Jan Wrzesinski","doi":"10.1016/j.ejcb.2024.151444","DOIUrl":"10.1016/j.ejcb.2024.151444","url":null,"abstract":"<div><p>Piwi proteins and Piwi interacting RNAs, piRNAs, presented in germline cells play a role in transposon silencing during germline development. In contrast, the role of somatic Piwi proteins and piRNAs still remains obscure. Here, we characterize the expression pattern and distribution of piRNAs in human renal cells in terms of their potential role in kidney development. Further, we show that all <em>PIWI</em> genes are expressed at the RNA level, however, only <em>PIWIL1</em> gene is detected at the protein level by western blotting in healthy and cancerous renal cells. So far, the expression of human Piwil1 protein has only been shown in testes and cancer cells, but not in healthy somatic cell lines. Since we observe only Piwil1 protein, the regulation of other <em>PIWI</em> genes is probably more intricated, and depends on environmental conditions. Next, we demonstrate that downregulation of Piwil1 protein results in a decrease in the rate of cell proliferation, while no change in the level of apoptotic cells is observed. Confocal microscopy analysis reveals that Piwil1 protein is located in both cellular compartments, cytoplasm and nucleus in renal cells. Interestingly, in nucleus region Piwil1 is observed close to the spindle during all phases of mitosis in all tested cell lines. It strongly indicates that Piwil1 protein plays an essential role in proliferation of somatic cells. Moreover, involvement of Piwil1 in cell division could, at least partly, explain invasion and metastasis of many types of cancer cells with upregulation of <em>PIWIL1</em> gene expression. It also makes Piwil1 protein as a potential target in the anticancer therapy.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151444"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017193352400061X/pdfft?md5=7451054a08e402ce6ec1ba62765123ed&pid=1-s2.0-S017193352400061X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636888","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":"Elimination of the extra chromosome of Dup15q syndrome iPSCs for cellular and molecular investigation","authors":"Haruka Munezane ,&nbsp;Keiko Imamura ,&nbsp;Naoko Fujimoto ,&nbsp;Akitsu Hotta ,&nbsp;Hiroshi Yukitake ,&nbsp;Haruhisa Inoue","doi":"10.1016/j.ejcb.2024.151446","DOIUrl":"10.1016/j.ejcb.2024.151446","url":null,"abstract":"<div><p>Chromosome 15q11.2–13.1 duplication (Dup15q) syndrome is one of the most common autism spectrum disorders (ASDs) associated with copy number variants (CNVs). For the analysis of CNV-relevant pathological cellular phenotypes, a CNV-corrected isogenic cell line is useful for excluding the influence of genetic background. Here, we devised a strategy to remove the isodicentric chromosome 15 by inserting a puro-ΔTK selection cassette into the extra chromosome using the CRISPR-Cas9 system, followed by a subsequent two-step drug selection. A series of assays, including qPCR-based copy number analysis and karyotype analysis, confirmed the elimination of the extra chromosome. Furthermore, cerebral organoids were generated from the parental Dup15q iPSCs and their isogenic iPSCs. scRNA-seq analysis revealed the alteration of expression levels in ion-channel-related genes and synapse-related genes in glutamatergic and GABAergic neurons in Dup15q organoids, respectively. The established isogenic cell line is a valuable resource for unraveling cellular and molecular alterations associated with Dup15q syndrome.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151446"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000633/pdfft?md5=544af3c06a8f5da20823c813cbf3db8d&pid=1-s2.0-S0171933524000633-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765820","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":"Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells","authors":"Salvatore Nesci ,&nbsp;Cristina Algieri ,&nbsp;Matteo Antonio Tallarida ,&nbsp;Rosita Stanzione ,&nbsp;Saverio Marchi ,&nbsp;Donatella Pietrangelo ,&nbsp;Fabiana Trombetti ,&nbsp;Luca D’Ambrosio ,&nbsp;Maurizio Forte ,&nbsp;Maria Cotugno ,&nbsp;Ilaria Nunzi ,&nbsp;Rachele Bigi ,&nbsp;Loredana Maiuolo ,&nbsp;Antonio De Nino ,&nbsp;Paolo Pinton ,&nbsp;Giovanni Romeo ,&nbsp;Speranza Rubattu","doi":"10.1016/j.ejcb.2024.151398","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151398","url":null,"abstract":"<div><p>Naringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The F₁F_O-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especially in the presence of Ca²⁺ cation used as cofactor. Indeed, NRG was a selective inhibitor of the hydrophilic F₁ domain displaying a binding site overlapped with quercetin in the inside surface of an annulus made by the three α and the three β subunits arranged alternatively in a hexamer. The kinetic constant of inhibition suggested that NRG preferred the enzyme activated by Ca²⁺ rather than the F₁F_O-ATPase activated by the natural cofactor Mg²⁺. From the inhibition type mechanism of NRG stemmed the possibility to speculate that NRG can prevent the activation of F₁F_O-ATPase by Ca²⁺. The event correlated to the protective role in the mitochondrial permeability transition pore opening by NRG as well as to the reduction of ROS production probably linked to the NRG chemical structure with antioxidant action. Moreover, in primary cerebral endothelial cells (ECs) obtained from stroke prone spontaneously hypertensive rats NRG had a protective effect on salt-induced injury by restoring cell viability and endothelial cell tube formation while also rescuing complex I activity.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151398"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000153/pdfft?md5=44a7a4ec51bf85a8291fe739ca43f7a5&pid=1-s2.0-S0171933524000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749326","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 small yeast GTPase Rho5 requires specific mitochondrial outer membrane proteins for translocation under oxidative stress and interacts with the VDAC Por1","authors":"Linnet Bischof,&nbsp;Franziska Schweitzer,&nbsp;Hans-Peter Schmitz,&nbsp;Jürgen J. Heinisch","doi":"10.1016/j.ejcb.2024.151405","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151405","url":null,"abstract":"<div><p>Yeast Rho5 is a small GTPase which mediates the response to nutrient and oxidative stress, and triggers mitophagy and apoptosis. We here studied the rapid translocation of a GFP-tagged Rho5 to mitochondria under such stress conditions by live-cell fluorescence microscopy in the background of strains lacking different mitochondrial outer membrane proteins (MOMP). Fun14, Msp1 and Alo1 were found to be required for efficient recruitment of the GTPase, whereas translocation of Dck1 and Lmo1, the subunits of its dimeric GDP/GTP exchange factor (GEF), remained unaffected. An influence of the voltage-dependent anion channel (VDAC) Por1 on the association of GFP-Rho5 with mitochondria under oxidative stress conditions appeared to be strain-dependent. However, epistasis analyses and bimolecular fluorescence complementation (BiFC) studies indicate a genetic and physical interaction. All four strains lacking a single MOMP were investigated for their effect on mitophagy.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151405"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000220/pdfft?md5=2d55ac6b32853bfa5e71c7b6ab106a18&pid=1-s2.0-S0171933524000220-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163207","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":"Olfactory receptors impact pathophysiological processes of lung diseases in bronchial epithelial cells","authors":"Daniel Weidinger ,&nbsp;Julian Jacobsen ,&nbsp;Desiree Alisch ,&nbsp;Hendrik Uebner ,&nbsp;Natalie Heinen ,&nbsp;Lea Greune ,&nbsp;Saskia Westhoven ,&nbsp;Kaschin Jamal Jameel ,&nbsp;Juliane Kronsbein ,&nbsp;Stephanie Pfaender ,&nbsp;Christian Taube ,&nbsp;Sebastian Reuter ,&nbsp;Marcus Peters ,&nbsp;Hanns Hatt ,&nbsp;Jürgen Knobloch","doi":"10.1016/j.ejcb.2024.151408","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151408","url":null,"abstract":"<div><h3>Background</h3><p>Therapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are limited. Bronchial epithelial cells are key in the pathogenesis by releasing the central proinflammatory cytokine interleukine-8 (IL-8). Olfactory receptors (ORs) are expressed in various cell types. This study examined the drug target potential of ORs by investigating their impact on associated pathophysiological processes in lung epithelial cells.</p></div><div><h3>Methods</h3><p>Experiments were performed in the A549 cell line and in primary human bronchial epithelial cells. OR expression was investigated using RT-PCR, Western blot, and immunocytochemical staining. OR-mediated effects were analyzed by measuring 1) intracellular calcium concentration via calcium imaging, 2) cAMP concentration by luminescence-based assays, 3) wound healing by scratch assays, 4) proliferation by MTS-based assays, 5) cellular vitality by Annexin V/PI-based FACS staining, and 6) the secretion of IL-8 in culture supernatants by ELISA.</p></div><div><h3>Results</h3><p>By screening 100 potential OR agonists, we identified two, Brahmanol and Cinnamaldehyde, that increased intracellular calcium concentrations. The mRNA and proteins of the corresponding receptors OR2AT4 and OR2J3 were detected. Stimulation of OR2J3 with Cinnamaldehyde reduced 1) IL-8 in the absence and presence of bacterial and viral pathogen-associated molecular patterns (PAMPs), 2) proliferation, and 3) wound healing but increased cAMP. In contrast, stimulation of OR2AT4 by Brahmanol increased wound healing but did not affect cAMP and proliferation. Both ORs did not influence cell vitality.</p></div><div><h3>Conclusion</h3><p>ORs might be promising drug target candidates for lung diseases with non-type 2 inflammation. Their stimulation might reduce inflammation or prevent tissue remodeling by promoting wound healing.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151408"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000256/pdfft?md5=e70d3f1f239a419f3746716aef60a9dd&pid=1-s2.0-S0171933524000256-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351823","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":"Role of the 3-mercaptopyruvate sulfurtransferase in colon/colorectal cancers","authors":"Katarina Matyasova ,&nbsp;Andrea Soltysova ,&nbsp;Petr Babula ,&nbsp;Olga Krizanova ,&nbsp;Veronika Liskova","doi":"10.1016/j.ejcb.2024.151415","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151415","url":null,"abstract":"<div><p>The 3-mercaptopyruvate sulfurtransferase (MPST) is a protein persulfidase, occurring mainly in mitochondria. Although function of this protein in cancer cells has been already studied, no clear outcome can be postulated up to now. Therefore, we focused on the determination of function of MPST in colon (HCT116 cells)/colorectal (DLD1 cells) cancers. <em>In silico</em> analysis revealed that in gastrointestinal cancers, MPST together with its binding partners can be either of a high risk or might have a protective effect. Silencing of <em>MPST</em> gene resulted in decreased ATP, while acetyl-CoA levels were elevated. Increased apoptosis was detected in cells with silenced <em>MPST</em> gene, which was accompanied by decrease in mitochondrial membrane potential, but no changes in IP₃ receptor’s protein. Mitochondria underwent activation of fission and elevated DRP1 expression after <em>MPST</em> silencing. Proliferation and migration of DLD1 and HCT116 cells were markedly affected, showing the importance of MPST protein in colon/colorectal cancer development.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151415"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000323/pdfft?md5=40bcbadcf22b02eeb742c65d27b13fae&pid=1-s2.0-S0171933524000323-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558767","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":"Crystal structure of NRAS Q61K with a ligand-induced pocket near switch II","authors":"Teklab Gebregiworgis ,&nbsp;Jonathan Yui-Lai Chan ,&nbsp;Douglas A. Kuntz ,&nbsp;Gilbert G. Privé ,&nbsp;Christopher B. Marshall ,&nbsp;Mitsuhiko Ikura","doi":"10.1016/j.ejcb.2024.151414","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151414","url":null,"abstract":"<div><p>The RAS isoforms (KRAS, HRAS and NRAS) have distinct cancer type-specific profiles. NRAS mutations are the second most prevalent RAS mutations in skin and hematological malignancies. Although RAS proteins were considered undruggable for decades, isoform and mutation-specific investigations have produced successful RAS inhibitors that are either specific to certain mutants, isoforms (pan-KRAS) or target all RAS proteins (pan-RAS). While extensive structural and biochemical investigations have focused mainly on K- and H-RAS mutations, NRAS mutations have received less attention, and the most prevalent NRAS mutations in human cancers, Q61K and Q61R, are rare in K- and H-RAS. This manuscript presents a crystal structure of the NRAS Q61K mutant in the GTP-bound form. Our structure reveals a previously unseen pocket near switch II induced by the binding of a ligand to the active form of the protein. This observation reveals a binding site that can potentially be exploited for development of inhibitors against mutant NRAS. Furthermore, the well-resolved catalytic site of this GTPase bound to native GTP provides insight into the stalled GTP hydrolysis observed for NRAS-Q61K.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151414"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000311/pdfft?md5=ff3510fc9ce1ff5ba8e4b90d8544a6d3&pid=1-s2.0-S0171933524000311-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620025","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":"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":"2024-06-01","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":"Septin-dependent defense mechanisms against Pseudomonas aeruginosa are stalled in cystic fibrosis bronchial epithelial cells","authors":"Sylvain Brax ,&nbsp;Clémence Gaudin ,&nbsp;Claire Calmel ,&nbsp;Pierre-Yves Boëlle ,&nbsp;Harriet Corvol ,&nbsp;Manon Ruffin ,&nbsp;Loïc Guillot","doi":"10.1016/j.ejcb.2024.151416","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151416","url":null,"abstract":"<div><p>Airway epithelial cells form a physical barrier against inhaled pathogens and coordinate innate immune responses in the lungs. Bronchial cells in people with cystic fibrosis (pwCF) are colonized by <em>Pseudomonas aeruginosa</em> because of the accumulation of mucus in the lower airways and an altered immune response. This leads to chronic inflammation, lung tissue damage, and accelerated decline in lung function. Thus, identifying the molecular factors involved in the host response in the airways is crucial for developing new therapeutic strategies. The septin (SEPT) cytoskeleton is involved in tissue barrier integrity and anti-infective responses. SEPT7 is critical for maintaining SEPT complexes and for sensing pathogenic microbes. In the lungs, SEPT7 may be involved in the epithelial barrier resistance to infection; however, its role in cystic fibrosis (CF) <em>P. aeruginosa</em> infection is unknown. This study aimed to investigate the role of SEPT7 in controlling <em>P. aeruginosa</em> infection in bronchial epithelial cells, particularly in CF. The study findings showed that SEPT7 encages <em>P. aeruginosa</em> in bronchial epithelial cells and its inhibition downregulates the expression of other SEPTs. In addition, <em>P. aeruginosa</em> does not regulate SEPT7 expression. Finally, we found that inhibiting SEPT7 expression in bronchial epithelial cells (BEAS-2B 16HBE14o- and primary cells) resulted in higher levels of internalized <em>P. aeruginosa</em> and decreased IL-6 production during infection, suggesting a crucial role of SEPT7 in the host response against this bacterium. However, these effects were not observed in the CF cells (16HBE14o-/F508del and primary cells) which may explain the persistence of infection in pwCF. The study findings suggest the modification of SEPT7 expression as a potential approach for the anti-infective control of <em>P. aeruginosa</em>, particularly in CF.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151416"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000335/pdfft?md5=ca8af7ea625def8665005329ab10adb1&pid=1-s2.0-S0171933524000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140605208","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":"Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles","authors":"Rebecca Holzapfel ,&nbsp;Agata Prell ,&nbsp;Fabian Schumacher ,&nbsp;Veronika Perschin ,&nbsp;José Pedro Friedmann Angeli ,&nbsp;Burkhard Kleuser ,&nbsp;Christian Stigloher ,&nbsp;Gholamreza Fazeli","doi":"10.1016/j.ejcb.2024.151411","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151411","url":null,"abstract":"<div><p>Efficient degradation of phagocytic cargo in lysosomes is crucial to maintain cellular homeostasis and defending cells against pathogens. However, the mechanisms underlying the degradation and recycling of macromolecular cargo within the phagolysosome remain incompletely understood. We previously reported that the phagolysosome containing the corpse of the polar body in <em>C. elegans</em> tubulates into small vesicles to facilitate corpse clearance, a process that requires cargo protein degradation and amino acid export. Here we show that degradation of hexosylceramides by the prosaposin ortholog SPP-10 and glucosylceramidases is required for timely corpse clearance. We observed accumulation of membranous structures inside endolysosomes of <em>spp-10-</em>deficient worms, which are likely caused by increased hexosylceramide species. <em>spp-10</em> deficiency also caused alteration of additional sphingolipid subclasses, like dihydroceramides, 2-OH-ceramides, and dihydrosphingomyelins. While corpse engulfment, initial breakdown of corpse membrane inside the phagolysosome and lumen acidification proceeded normally in <em>spp-10</em>-deficient worms, formation of the cargo-containing vesicles from the corpse phagolysosome was reduced, resulting in delayed cargo degradation and phagolysosome resolution. Thus, by combining ultrastructural studies and sphingolipidomic analysis with observing single phagolysosomes over time, we identified a role of prosaposin/SPP-10 in maintaining phagolysosomal structure, which promotes efficient resolution of phagocytic cargos.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151411"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000281/pdfft?md5=563757f509a0ea66504431e4104977e6&pid=1-s2.0-S0171933524000281-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351824","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}