European journal of cell biology最新文献

{"title":"Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells","authors":"Caroline Diener ,&nbsp;Konstantin Thüre ,&nbsp;Annika Engel ,&nbsp;Martin Hart ,&nbsp;Andreas Keller ,&nbsp;Eckart Meese ,&nbsp;Ulrike Fischer","doi":"10.1016/j.ejcb.2024.151458","DOIUrl":"10.1016/j.ejcb.2024.151458","url":null,"abstract":"<div><div>Mesenchymal Stem Cells (MSCs) derived from the embryonic mesoderm persist as a viable source of multipotent cells in adults and have a crucial role in tissue repair. One of the most promising aspects of MSCs is their ability to trans-differentiate into cell types outside of the mesodermal lineage, such as neurons. This characteristic positions MSCs as potential therapeutic tools for neurological disorders. However, the definition of a clear MSC signature is an ongoing topic of debate. Likewise, there is still a significant knowledge gap about functional alterations of MSCs during their transition to a neural fate. In this study, our focus is on the dynamic expression of RNA in MSCs as they undergo trans-differentiation compared to undifferentiated MSCs. To track and correlate changes in cellular signaling, we conducted high-throughput RNA expression profiling during the early time-course of human MSC neurogenic trans-differentiation. The expression of synapse maturation markers, including <em>NLGN2</em> and <em>NPTX1</em>, increased during the first 24 h. The expression of neuron differentiation markers, such as <em>GAP43</em> strongly increased during 48 h of trans-differentiation. Neural stem cell marker <em>NES</em> and neuron differentiation marker, including <em>TUBB3</em> and <em>ENO1</em>, were highly expressed in mesenchymal stem cells and remained so during trans-differentiation. Pathways analyses revealed early changes in MSCs signaling that can be linked to the acquisition of neuronal features. Furthermore, we identified microRNAs (miRNAs) as potential drivers of the cellular trans-differentiation process. We also determined potential risk factors related to the neural trans-differentiation process. These factors include the persistence of stemness features and the expression of factors involved in neurofunctional abnormalities and tumorigenic processes. In conclusion, our findings contribute valuable insights into the intricate landscape of MSCs during neural trans-differentiation. These insights can pave the way for the development of safer treatments of neurological disorders.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151458"},"PeriodicalIF":4.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327003","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":"Insulin receptor substrate 1 is a novel member of EGFR signaling in pancreatic cells","authors":"Tamás Takács ,&nbsp;Loretta László ,&nbsp;Álmos Tilajka ,&nbsp;Julianna Novák ,&nbsp;László Buday ,&nbsp;Virag Vas","doi":"10.1016/j.ejcb.2024.151457","DOIUrl":"10.1016/j.ejcb.2024.151457","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma is an extremely incurable cancer type characterized by cells with highly proliferative capacity and resistance against the current therapeutic options. Our study reveals that IRS1 acts as a bridging molecule between EGFR and IGFR/InsR signalization providing a potential mechanism for the interplay between signaling pathways and bypassing EGFR-targeted or IGFR/InsR-targeted therapies. The analysis of IRS1 phosphorylation status in four pancreatic cell lines identified the impact of EGFR signaling on IRS1 activation in comparison with InsR/IGFR signaling. Significantly reduced viability was observed in IRS1-silenced cells even upon EGF stimulation showing the critical role of IRS1 in the EGFR signaling network in both malignant and normal pancreatic cells. This study also demonstrated that EGFR binds directly to IRS1 and at least on two tyrosine sites, Y612 and Y896, IRS1 becomes phosphorylated in response to EGF stimulation. Mechanistically, the EGFR-mediated phosphorylation of IRS1 can further activate the MAPK signaling pathway with the recruitment of GRB2 protein. Collectively, in this study, IRS1 was identified as a crucial regulator in the EGFR signaling suggesting IRS1 as a potential target for more durable responses to targeted PDAC therapy.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151457"},"PeriodicalIF":4.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319543","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":"Androgen receptor activation inhibits endothelial cell migration in vitro and angiogenesis in vivo","authors":"Yen-Nien Huo ,&nbsp;Hsiang-Yu Yang ,&nbsp;Hung-Yen Ke ,&nbsp;Chih-Yuan Lin ,&nbsp;Chien-Sung Tsai","doi":"10.1016/j.ejcb.2024.151456","DOIUrl":"10.1016/j.ejcb.2024.151456","url":null,"abstract":"<div><p>Our previous research revealed that androgen receptor (AR) activation reduces endothelial cell proliferation via non-genomic pathways. We hypothesized that AR activation might also affect endothelial cell migration, a critical step in angiogenesis. Our data demonstrates that treatment of human umbilical vein endothelial cells (HUVECs) with AR agonists, metribolone (R1881) or dihydrotestosterone (DHT), results in a dose-dependent reduction in migration, which can be reversed by AR antagonists or AR knockdown. Mechanistically, R1881 inhibits HUVEC migration by suppressing RhoA activity through the cSrc/FAK/paxillin pathway and promoting RhoA degradation via RhoA-p27 complex formation, ultimately resulting in RhoA ubiquitination. Transfection with constitutively active RhoA-V14 rescues the inhibitory effect of R1881 on HUVEC migration. Furthermore, R1881 elevates intracellular vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) levels but reduces VEGF secretion from HUVECs. This reduction is attributed to the formation of VEGF-CTGF complexes in the cytosol induced by R1881. Transfection with RhoA-V14 reduces CTGF levels and VEGF-CTGF complex formation, leading to enhanced VEGF secretion. Pre-treatment with WP631, a CTGF inhibitor, mitigates the R1881-induced reduction in VEGF secretion and HUVECs migration. In vivo assessments using zebrafish angiogenesis and mouse matrigel plug assays validate the anti-angiogenic effects of R1881. These findings provide insight into the molecular mechanisms through which AR activation modulates endothelial cell migration and angiogenesis.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151456"},"PeriodicalIF":4.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000736/pdfft?md5=d810f7b09670b347a00ba56406f43b8d&pid=1-s2.0-S0171933524000736-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242280","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 point-of-research decision in synovial tissue engineering: Mesenchymal stromal cells, tissue derived fibroblast or CTGF-mediated mesenchymal-to-fibroblast transition","authors":"Alexandra Damerau ,&nbsp;Marieluise Kirchner ,&nbsp;Philipp Mertins ,&nbsp;Frank Buttgereit ,&nbsp;Timo Gaber","doi":"10.1016/j.ejcb.2024.151455","DOIUrl":"10.1016/j.ejcb.2024.151455","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent inflammatory joint diseases characterized by synovitis, cartilage, and bone destruction. Fibroblast-like synoviocytes (FLSs) of the synovial membrane are a decisive factor in arthritis, making them a target for future therapies. Developing novel strategies targeting FLSs requires advanced <em>in vitro</em> joint models that accurately replicate non-diseased joint tissue. This study aims to identify a cell source reflecting physiological synovial fibroblasts. Therefore, we newly compared the phenotype and metabolism of “healthy” knee-derived FLSs from patients with ligament injuries (trauma-FLSs) to mesenchymal stromal cells (MSCs), their native precursors. We differentiated MSCs into fibroblasts using connective tissue growth factor (CTGF) and compared selected protein and gene expression patterns to those obtained from trauma-FLSs and OA-FLSs. Based on these findings, we explored the potential of an MSC-derived synovial tissue model to simulate a chronic inflammatory response akin to that seen in arthritis. We have identified MSCs as a suitable cell source for synovial tissue engineering because, despite metabolic differences, they closely resemble human trauma-derived FLSs. CTGF-mediated differentiation of MSCs increased <em>HAS2</em> expression, essential for hyaluronan synthesis. It showed protein expression patterns akin to OA-FLSs, including markers of ECM components and fibrosis, and enzymes leading to a shift in metabolism towards increased fatty acid oxidation. In general, cytokine stimulation of MSCs in a synovial tissue model induced pro-inflammatory and pro-angiogenic gene expression, hyperproliferation, and increased glucose consumption, reflecting cellular response in human arthritis. We conclude that MSCs can serve as a proxy to study physiological synovial processes and inflammatory responses. In addition, CTGF-mediated mesenchymal-to-fibroblast transition resembles OA-FLSs. Thus, we emphasize MSCs as a valuable cell source for tools in preclinical drug screening and their application in tissue engineering.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151455"},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000724/pdfft?md5=dc4d54feecbd974e4dfb070a695b3639&pid=1-s2.0-S0171933524000724-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242283","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 cholesterol biosynthesis by CTCF and H3K27 methylation is critical for cell migration","authors":"Lukasz Stanislaw Kaczmarczyk ,&nbsp;Dagmawit Babele ,&nbsp;Nehora Levi ,&nbsp;Gowthaman Gunasekaran ,&nbsp;Mali Salmon-Divon ,&nbsp;Gabi Gerlitz","doi":"10.1016/j.ejcb.2024.151454","DOIUrl":"10.1016/j.ejcb.2024.151454","url":null,"abstract":"<div><p>CTCF is a key factor in three-dimensional chromatin folding and transcriptional control that was found to affect cancer cell migration by a mechanism that is still poorly understood. To identify this mechanism, we used mouse melanoma cells with a partial loss of function (pLoF) of CTCF. We found that CTCF pLoF inhibits cell migration rate while leading to an increase in the expression of multiple enzymes in the cholesterol biosynthesis pathway along with an elevation in the cellular cholesterol level. In agreement with the cholesterol change we detected altered membrane dynamics in CTCF pLoF cells as measured by reduced formation of migrasomes, extracellular vesicles formed at the rear side of migrating cells. Inhibition of cholesterol synthesis in CTCF pLoF cells restored the cellular migration rate and migrasome formation, suggesting that CTCF supports cell migration by suppressing cholesterol synthesis. Detailed analysis of the promoter of <em>Hmgcs1</em>, an early enzyme in the cholesterol synthesis pathway, revealed that CTCF prevents formation of a loop between that promoter and another promoter 200 kb away. CTCF also supports PRC2 recruitment to the promoter and deposition of H3K27me3. H3K27me3 at the promoter of <em>Hmgcs1</em> prevents SREBP2 binding and activation of transcription. By this mechanism, CTCF fine-tunes cholesterol levels to support cell migration. Notably, genome wide association studies suggest a link between CTCF and cholesterol-associated diseases, thus CTCF emerges as a new regulator of cholesterol biosynthesis.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151454"},"PeriodicalIF":4.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000712/pdfft?md5=0577d7a701c222841e742a834060ce91&pid=1-s2.0-S0171933524000712-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129020","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":"JAK activity regulates mesoderm cell fate by controlling MESP1 expression","authors":"Su Yao ,&nbsp;Yalin Zhu ,&nbsp;Fenglian He ,&nbsp;Min Yuan ,&nbsp;Rui Jiang ,&nbsp;Hongjie Zhang ,&nbsp;Yanbin Fu ,&nbsp;Ke Wei","doi":"10.1016/j.ejcb.2024.151452","DOIUrl":"10.1016/j.ejcb.2024.151452","url":null,"abstract":"<div><p>Cardiac development requires precise gene expression programs at each developmental stage guided by multiple signaling pathways and transcription factors (TFs). MESP1 is transiently expressed in mesoderm, and is essential for subsequent cardiac development, while the precise mechanism regulating its own transcription and mesoderm cell fate is not fully understood. Therefore, we developed a high content screen assay to identify regulators of MESP1 expression in mesodermal cells differentiated from human pluripotent stem cells (hPSCs). The screen identified CYT387, a JAK1/JAK2 kinase inhibitor, as a potent activator of MESP1 expression, which was also found to promote cardiomyocyte differentiation <em>in vitro</em>. Mechanistic studies found that JAK inhibition promotes MESP1 expression by reducing cytoplasmic calcium concentration and subsequently activating canonical WNT signaling. Our study identified a role of JAK signaling in early mesodermal cells, and sheds light on the connection between the JAK-STAT pathway and transcriptional regulation of MESP1, which expands our understanding of mesoderm and cardiac development.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151452"},"PeriodicalIF":4.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000694/pdfft?md5=52f210f6e16efdf5868a374965a7a6ba&pid=1-s2.0-S0171933524000694-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050283","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":"Investigating human monocyte adhesion, migration and transmigration and their modulation by Zika virus","authors":"Emma Partiot ,&nbsp;Diana Brychka ,&nbsp;Raphael Gaudin","doi":"10.1016/j.ejcb.2024.151453","DOIUrl":"10.1016/j.ejcb.2024.151453","url":null,"abstract":"<div><p>Human circulating monocytes are established targets for Zika virus (ZIKV) infection. Because of their important migratory properties toward any tissues, including the central nervous system (CNS), a better understanding of the mechanisms underlying monocyte transmigration upon ZIKV infection is required. Here, we monitored adhesion, migration and transmigration properties of monocytes exposed to ZIKV. We found that ZIKV enhanced monocyte adhesion on collagen compared to mock-exposed samples, and that pharmacological inhibition of mDia and Cdc42 function induced a significant decrease of adhesion in both mock- and ZIKV-exposed monocytes. In contrast, monocyte migration through collagen was inhibited by most of the tested small molecules targeting regulators of actin polymerization, including Rac1, ROCK, Cdc42, mDia, Arp2/3, Myosin-II and LFA-1. ZIKV-exposed monocyte migration showed a very similar profile to that of their mock-exposed counterparts. Finally, assessment of monocyte transmigration through human cerebral microvascular endothelial cells (hCMEC/D3) showed dependency on Rac1, ROCK, and Cdc42, independently of their infection status. In contrast, we identified that BIRT377, an antagonist of LFA-1, significantly inhibited transmigration of ZIKV-exposed but not mock-exposed monocytes. As BIRT377 increased adhesion of ZIKV-exposed monocytes, we propose that LFA-1 might be involved in a post-adhesion step to enhance viro-induced transmigration. These data suggest that ZIKV exposure triggers specific migratory properties of monocytes that are not exploited under physiological conditions. This work provides further insights on virus-host interactions important for viral neuroinvasion and offers novel targets to specifically inhibit the infiltration of infected cells to the CNS.</p></div><div><h3>Summary sentence</h3><p>Monocyte transmigration involves massive actin cytoskeleton reorganization regulated by small Rho GTPases and integrins, which can be subverted by viruses.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151453"},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000700/pdfft?md5=bc60d3ec29449637c36a037e6988c7b8&pid=1-s2.0-S0171933524000700-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050284","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":"Stable laminar shear stress induces G1 cell cycle arrest and autophagy in urothelial carcinoma by a torque sensor-coupled cone-and-plate device","authors":"Sheng-Yuan Huang ,&nbsp;Tien-Ssu Yu ,&nbsp;Jiun-Han Lin ,&nbsp;Wei-Hung Liu ,&nbsp;Chih-Ang Chung ,&nbsp;Yu-Che Cheng","doi":"10.1016/j.ejcb.2024.151451","DOIUrl":"10.1016/j.ejcb.2024.151451","url":null,"abstract":"<div><p>The microenvironments of urinary systems play crucial roles in the development and metastasis of cancers due to their generation of complex temporal and spatial fluidic profiles. Because of their versatility in creating desired biomimetic flow, cone-and-plate bioreactors offer great potential for bladder cancer research. In this study, we construct a biocompatible cone-and-plate device coupled with a torque sensor, enabling the application and real-time monitoring of stable shear stress up to 50 dyne/cm². Under a stable shear stress stimulation at 12 dyne/cm², bladder cancer cell BFTC-905 is arrested at the G1 phase with decreased cell proliferation after 24-hour treatment. This effect is associated with increased cyclin-dependent kinase inhibitors p21 and p27, inhibiting cyclin D1/CDK4 complex with dephosphorylation of serine 608 on the retinoblastoma protein. Consequently, an increase in cyclin D3 and decreases in cyclin A2 and cyclin E2 are observed. Moreover, we demonstrate that the shear stress stimulation upregulates the expression of autophagy-related proteins Beclin-1, LC3B-I and LC3B-II, while caspase cleavages are not activated under the same condition. The design of this system and its application shed new light on flow-induced phenomena in the study of urothelial carcinomas.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151451"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000682/pdfft?md5=776e1ba357f13ec2586634065d8583c9&pid=1-s2.0-S0171933524000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095438","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":"Generating kidney organoids based on developmental nephrology","authors":"Yutaro Ibi,&nbsp;Ryuichi Nishinakamura","doi":"10.1016/j.ejcb.2024.151450","DOIUrl":"10.1016/j.ejcb.2024.151450","url":null,"abstract":"<div><p>Over the past decade, the induction protocols for the two types of kidney organoids (nephron organoids and ureteric bud organoids) from pluripotent stem cells (PSCs) have been established based on the knowledge gained in developmental nephrology. Kidney organoids are now used for disease modeling and drug screening, but they also have potential as tools for clinical transplantation therapy. One of the options to achieve this goal would be to assemble multiple renal progenitor cells (nephron progenitor, ureteric bud, stromal progenitor) to reproduce the organotypic kidney structure from PSCs. At least from mouse PSCs, all the three progenitors have been induced and assembled into such “higher order” kidney organoids. We will provide an overview of the developmental nephrology required for the induction of renal progenitors and discuss recent advances and remaining challenges of kidney organoids for clinical transplantation therapy.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151450"},"PeriodicalIF":4.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000670/pdfft?md5=19fbc7d41b11a8bbb7a13ed75c5ac68f&pid=1-s2.0-S0171933524000670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975373","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":"Salmonella infection impacts host proteome thermal stability","authors":"Marlène S. Birk ,&nbsp;Philipp Walch ,&nbsp;Tarik Baykara ,&nbsp;Stephanie Sefried ,&nbsp;Jan Amelang ,&nbsp;Elena Buerova ,&nbsp;Ingrid Breuer ,&nbsp;Jörg Vervoorts ,&nbsp;Athanasios Typas ,&nbsp;Mikhail M. Savitski ,&nbsp;André Mateus ,&nbsp;Joel Selkrig","doi":"10.1016/j.ejcb.2024.151448","DOIUrl":"10.1016/j.ejcb.2024.151448","url":null,"abstract":"<div><p>Intracellular bacterial pathogens hijack the protein machinery of infected host cells to evade their defenses and cultivate a favorable intracellular niche. The intracellular pathogen <em>Salmonella enterica</em> subsp. Typhimurium (<em>S</em>Tm) achieves this by injecting a cocktail of effector proteins into host cells that modify the activity of target host proteins. Yet, proteome-wide approaches to systematically map changes in host protein function during infection have remained challenging. Here we adapted a functional proteomics approach - Thermal-Proteome Profiling (TPP) - to systematically assess proteome-wide changes in host protein abundance and thermal stability throughout an <em>S</em>Tm infection cycle. By comparing macrophages treated with live or heat-killed <em>S</em>Tm, we observed that most host protein abundance changes occur independently of <em>S</em>Tm viability. In contrast, a large portion of host protein thermal stability changes were specific to infection with live <em>S</em>Tm. This included pronounced thermal stability changes in proteins linked to mitochondrial function (Acod1/Irg1, Cox6c, Samm50, Vdac1, and mitochondrial respiratory chain complex proteins), as well as the interferon-inducible protein with tetratricopeptide repeats, Ifit1. Integration of our TPP data with a publicly available <em>S</em>Tm-host protein-protein interaction database led us to discover that the secreted <em>S</em>Tm effector kinase, SteC, thermally destabilizes and phosphorylates the ribosomal preservation factor Serbp1. In summary, this work emphasizes the utility of measuring protein thermal stability during infection to accelerate the discovery of novel molecular interactions at the host-pathogen interface.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151448"},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000657/pdfft?md5=0165df0c33e474067e594538a5fed8cd&pid=1-s2.0-S0171933524000657-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916423","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}