eLife最新文献 - Book学术

Cytosolic and endoplasmic reticulum chaperones inhibit wt-p53 to increase cancer cells' survival by refluxing ER-proteins to the cytosol.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-09 DOI: 10.7554/eLife.102658

Salam Dabsan, Gali Zur, Naim Abu-Freha, Shahar Sofer, Iris Grossman-Haham, Ayelet Gilad, Aeid Igbaria

{"title":"Cytosolic and endoplasmic reticulum chaperones inhibit wt-p53 to increase cancer cells' survival by refluxing ER-proteins to the cytosol.","authors":"Salam Dabsan, Gali Zur, Naim Abu-Freha, Shahar Sofer, Iris Grossman-Haham, Ayelet Gilad, Aeid Igbaria","doi":"10.7554/eLife.102658","DOIUrl":"https://doi.org/10.7554/eLife.102658","url":null,"abstract":"The endoplasmic reticulum (ER) is an essential sensing organelle responsible for the folding and secretion of almost one-third of eukaryotic cells' total proteins. However, environmental, chemical, and genetic insults often lead to protein misfolding in the ER, accumulating misfolded proteins, and causing ER stress. To solve this, several mechanisms were reported to relieve ER stress by decreasing the ER protein load. Recently, we reported a novel ER surveillance mechanism by which proteins from the secretory pathway are refluxed to the cytosol to relieve the ER of its content. The refluxed proteins gain new prosurvival functions in cancer cells, thereby increasing cancer cell fitness. We termed this phenomenon ER to CYtosol Signaling (or 'ERCYS'). Here, we found that in mammalian cells, ERCYS is regulated by DNAJB12, DNAJB14, and the HSC70 cochaperone SGTA. Mechanistically, DNAJB12 and DNAJB14 bind HSC70 and SGTA - through their cytosolically localized J-domains to facilitate ER-protein reflux. DNAJB12 is necessary and sufficient to drive this phenomenon to increase AGR2 reflux and inhibit wt-p53 during ER stress. Mutations in DNAJB12/14 J-domain prevent the inhibitory interaction between AGR2-wt-p53. Thus, targeting the DNAJB12/14-HSC70/SGTA axis is a promising strategy to inhibit ERCYS and impair cancer cell fitness.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeated activation of preoptic area recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional valence and hyperarousal states.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-09 DOI: 10.7554/eLife.101302

Zhiping Cao, Wing-Ho Yung, Ya Ke

{"title":"Repeated activation of preoptic area recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional valence and hyperarousal states.","authors":"Zhiping Cao, Wing-Ho Yung, Ya Ke","doi":"10.7554/eLife.101302","DOIUrl":"https://doi.org/10.7554/eLife.101302","url":null,"abstract":"Mental and behavioral disorders are associated with extended period of hot weather as found in heatwaves, but the underlying neural circuit mechanism remains poorly known. The posterior paraventricular thalamus (pPVT) is a hub for emotional processing and receives inputs from the hypothalamic preoptic area (POA), the well-recognized thermoregulation center. The present study was designed to explore whether chronic heat exposure leads to aberrant activities in POA recipient pPVT neurons and subsequent changes in emotional states. By devising an air heating paradigm mimicking the condition of heatwaves and utilizing emotion-related behavioral tests, viral tract tracing, in vivo calcium recordings, optogenetic manipulations, and electrophysiological recordings, we found that chronic heat exposure for 3 weeks led to negative emotional valence and hyperarousal states in mice. The pPVT neurons receive monosynaptic excitatory and inhibitory innervations from the POA. These neurons exhibited a persistent increase in neural activity following chronic heat exposure, which was essential for chronic heat-induced emotional changes. Notably, these neurons were also prone to display stronger neuronal activities associated with anxiety responses to stressful situations. Furthermore, we observed saturated neuroplasticity in the POA-pPVT excitatory pathway after chronic heat exposure that occluded further potentiation. Taken together, long-term aberration in the POA to pPVT pathway offers a neurobiological mechanism of emotional and behavioral changes seen in extended periods of hot weather like heatwaves.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Numb provides a fail-safe mechanism for intestinal stem cell self-renewal in adult Drosophila midgut.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-09 DOI: 10.7554/eLife.104723

Mengjie Li, Aiguo Tian, Jin Jiang

{"title":"Numb provides a fail-safe mechanism for intestinal stem cell self-renewal in adult Drosophila midgut.","authors":"Mengjie Li, Aiguo Tian, Jin Jiang","doi":"10.7554/eLife.104723","DOIUrl":"https://doi.org/10.7554/eLife.104723","url":null,"abstract":"Stem cell self-renewal often relies on asymmetric fate determination governed by niche signals and/or cell-intrinsic factors but how these regulatory mechanisms cooperate to promote asymmetric fate decision remains poorly understood. In adult Drosophila midgut, asymmetric Notch (N) signaling inhibits intestinal stem cell (ISC) self-renewal by promoting ISC differentiation into enteroblast (EB). We have previously shown that epithelium-derived Bone Morphogenetic Protein (BMP) promotes ISC self-renewal by antagonizing N pathway activity (Tian and Jiang, 2014). Here, we show that loss of BMP signaling results in ectopic N pathway activity even when the N ligand Delta (Dl) is depleted, and that the N inhibitor Numb acts in parallel with BMP signaling to ensure a robust ISC self-renewal program. Although Numb is asymmetrically segregated in about 80% of dividing ISCs, its activity is largely dispensable for ISC fate determination under normal homeostasis. However, Numb becomes crucial for ISC self-renewal when BMP signaling is compromised. Whereas neither Mad RNA interference nor its hypomorphic mutation led to ISC loss, inactivation of Numb in these backgrounds resulted in stem cell loss due to precocious ISC-to-EB differentiation. Furthermore, we find that numb mutations resulted in stem cell loss during midgut regeneration in response to epithelial damage that causes fluctuation in BMP pathway activity, suggesting that the asymmetrical segregation of Numb into the future ISC may provide a fail-save mechanism for ISC self-renewal by offsetting BMP pathway fluctuation, which is important for ISC maintenance in regenerative guts.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-09 DOI: 10.7554/eLife.104725

Conor J Howard, Nathan S Abell, Beatriz A Osuna, Eric M Jones, Leon Y Chan, Henry Chan, Dean R Artis, Jonathan B Asfaha, Joshua S Bloom, Aaron R Cooper, Andrew Liao, Eden Mahdavi, Nabil Mohammed, Alan L Su, Giselle A Uribe, Sriram Kosuri, Diane E Dickel, Nathan B Lubock

{"title":"High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery.","authors":"Conor J Howard, Nathan S Abell, Beatriz A Osuna, Eric M Jones, Leon Y Chan, Henry Chan, Dean R Artis, Jonathan B Asfaha, Joshua S Bloom, Aaron R Cooper, Andrew Liao, Eden Mahdavi, Nabil Mohammed, Alan L Su, Giselle A Uribe, Sriram Kosuri, Diane E Dickel, Nathan B Lubock","doi":"10.7554/eLife.104725","DOIUrl":"https://doi.org/10.7554/eLife.104725","url":null,"abstract":"Deep Mutational Scanning (DMS) is an emerging method to systematically test the functional consequences of thousands of sequence changes to a protein target in a single experiment. Because of its utility in interpreting both human variant effects and protein structure-function relationships, it holds substantial promise to improve drug discovery and clinical development. However, applications in this domain require improved experimental and analytical methods. To address this need, we report novel DMS methods to precisely and quantitatively interrogate disease-relevant mechanisms, protein-ligand interactions, and assess predicted response to drug treatment. Using these methods, we performed a DMS of the melanocortin-4 receptor (MC4R), a G-protein-coupled receptor (GPCR) implicated in obesity and an active target of drug development efforts. We assessed the effects of >6600 single amino acid substitutions on MC4R's function across 18 distinct experimental conditions, resulting in >20 million unique measurements. From this, we identified variants that have unique effects on MC4R-mediated Gαs- and Gαq-signaling pathways, which could be used to design drugs that selectively bias MC4R's activity. We also identified pathogenic variants that are likely amenable to a corrector therapy. Finally, we functionally characterized structural relationships that distinguish the binding of peptide versus small molecule ligands, which could guide compound optimization. Collectively, these results demonstrate that DMS is a powerful method to empower drug discovery and development.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-08 DOI: 10.7554/eLife.98023

Marketa Jirouskova, Karel Harant, Pavel Cejnar, Srikant Ojha, Katerina Korelova, Lenka Sarnova, Eva Sticova, Christoph H Mayr, Herbert B Schiller, Martin Gregor

{"title":"Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis.","authors":"Marketa Jirouskova, Karel Harant, Pavel Cejnar, Srikant Ojha, Katerina Korelova, Lenka Sarnova, Eva Sticova, Christoph H Mayr, Herbert B Schiller, Martin Gregor","doi":"10.7554/eLife.98023","DOIUrl":"10.7554/eLife.98023","url":null,"abstract":"Accumulation of extracellular matrix (ECM) in liver fibrosis is associated with changes in protein abundance and composition depending upon etiology of the underlying liver disease. Current efforts to unravel etiology-specific mechanisms and pharmacological targets rely on several models of experimental fibrosis. Here, we characterize and compare dynamics of hepatic proteome remodeling during fibrosis development and spontaneous healing in experimental mouse models of hepatotoxic (carbon tetrachloride [CCl4] intoxication) and cholestatic (3,5-diethoxycarbonyl-1,4-dihydrocollidine [DDC] feeding) injury. Using detergent-based tissue extraction and mass spectrometry, we identified compartment-specific changes in the liver proteome with detailed attention to ECM composition and changes in protein solubility. Our analysis revealed distinct time-resolved CCl4 and DDC signatures, with identified signaling pathways suggesting limited healing and a potential for carcinogenesis associated with cholestasis. Correlation of protein abundance profiles with fibrous deposits revealed extracellular chaperone clusterin with implicated role in fibrosis resolution. Dynamics of clusterin expression was validated in the context of human liver fibrosis. Atomic force microscopy of fibrotic livers complemented proteomics with profiles of disease-associated changes in local liver tissue mechanics. This study determined compartment-specific proteomic landscapes of liver fibrosis and delineated etiology-specific ECM components, providing thus a foundation for future antifibrotic therapies.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-08 DOI: 10.7554/eLife.101606

Alannah Lejeune, Chunyi Zhou, Defne Ercelen, Gregory Putzel, Xiaomin Yao, Alyson R Guy, Miranda Pawline, Magdalena Podkowik, Alejandro Pironti, Victor J Torres, Bo Shopsin, Ken Cadwell

{"title":"Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent.","authors":"Alannah Lejeune, Chunyi Zhou, Defne Ercelen, Gregory Putzel, Xiaomin Yao, Alyson R Guy, Miranda Pawline, Magdalena Podkowik, Alejandro Pironti, Victor J Torres, Bo Shopsin, Ken Cadwell","doi":"10.7554/eLife.101606","DOIUrl":"10.7554/eLife.101606","url":null,"abstract":"Gastrointestinal (GI) colonization by methicillin-resistant Staphylococcus aureus (MRSA) is associated with a high risk of transmission and invasive disease in vulnerable populations. The immune and microbial factors that permit GI colonization remain unknown. Male sex is correlated with enhanced Staphylococcus aureus nasal carriage, skin and soft tissue infections, and bacterial sepsis. Here, we established a mouse model of sexual dimorphism during GI colonization by MRSA. Our results show that in contrast to male mice that were susceptible to persistent colonization, female mice rapidly cleared MRSA from the GI tract following oral inoculation in a manner dependent on the gut microbiota. This colonization resistance displayed by female mice was mediated by an increase in IL-17A+ CD4+ T cells (Th17) and dependent on neutrophils. Ovariectomy of female mice increased MRSA burden, but gonadal female mice that have the Y chromosome retained enhanced Th17 responses and colonization resistance. Our study reveals a novel intersection between sex and gut microbiota underlying colonization resistance against a major widespread pathogen.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coordinated regulation of chemotaxis and resistance to copper by CsoR in Pseudomonas putida.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-08 DOI: 10.7554/eLife.100914

Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, Wenli Chen

{"title":"Coordinated regulation of chemotaxis and resistance to copper by CsoR in Pseudomonas putida.","authors":"Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, Wenli Chen","doi":"10.7554/eLife.100914","DOIUrl":"10.7554/eLife.100914","url":null,"abstract":"Copper is an essential enzyme cofactor in bacteria, but excess copper is highly toxic. Bacteria can cope with copper stress by increasing copper resistance and initiating chemorepellent response. However, it remains unclear how bacteria coordinate chemotaxis and resistance to copper. By screening proteins that interacted with the chemotaxis kinase CheA, we identified a copper-binding repressor CsoR that interacted with CheA in Pseudomonas putida. CsoR interacted with the HPT (P1), Dimer (P3), and HATPase_c (P4) domains of CheA and inhibited CheA autophosphorylation, resulting in decreased chemotaxis. The copper-binding of CsoR weakened its interaction with CheA, which relieved the inhibition of chemotaxis by CsoR. In addition, CsoR bound to the promoter of copper-resistance genes to inhibit gene expression, and copper-binding released CsoR from the promoter, leading to increased gene expression and copper resistance. P. putida cells exhibited a chemorepellent response to copper in a CheA-dependent manner, and CsoR inhibited the chemorepellent response to copper. Besides, the CheA-CsoR interaction also existed in proteins from several other bacterial species. Our results revealed a mechanism by which bacteria coordinately regulated chemotaxis and resistance to copper by CsoR.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing. 通过脱氨酶和读取蛋白辅助测序在整个转录组鉴定 5-甲基胞嘧啶。

IF 6.4 1区生物学

eLife Pub Date : 2025-04-08 DOI: 10.7554/eLife.98166

Jiale Zhou, Ding Zhao, Jinze Li, Deqiang Kong, Xiangrui Li, Renquan Zhang, Yuru Liang, Xun Gao, Yuqiang Qian, Di Wang, Jiahui Chen, Liangxue Lai, Yang Han, Zhanjun Li

{"title":"Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing.","authors":"Jiale Zhou, Ding Zhao, Jinze Li, Deqiang Kong, Xiangrui Li, Renquan Zhang, Yuru Liang, Xun Gao, Yuqiang Qian, Di Wang, Jiahui Chen, Liangxue Lai, Yang Han, Zhanjun Li","doi":"10.7554/eLife.98166","DOIUrl":"10.7554/eLife.98166","url":null,"abstract":"5-Methylcytosine (m5C) is one of the posttranscriptional modifications in mRNA and is involved in the pathogenesis of various diseases. However, the capacity of existing assays for accurately and comprehensively transcriptome-wide m5C mapping still needs improvement. Here, we develop a detection method named DRAM (deaminase and reader protein assisted RNA methylation analysis), in which deaminases (APOBEC1 and TadA-8e) are fused with m5C reader proteins (ALYREF and YBX1) to identify the m5C sites through deamination events neighboring the methylation sites. This antibody-free and bisulfite-free approach provides transcriptome-wide editing regions which are highly overlapped with the publicly available bisulfite-sequencing (BS-seq) datasets and allows for a more stable and comprehensive identification of the m5C loci. In addition, DRAM system even supports ultralow input RNA (10 ng). We anticipate that the DRAM system could pave the way for uncovering further biological functions of m5C modifications.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Connecting the dots: Managing species interaction networks to mitigate the impacts of global change.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-08 DOI: 10.7554/eLife.98899

Luis Abdala-Roberts, Adriana Puentes, Deborah L Finke, Robert J Marquis, Marta Montserrat, Erik H Poelman, Sergio Rasmann, Arnaud Sentis, Celia C Symons, Nicole M van Dam, Gina Wimp, Christer Björkman, Kailen A Mooney

{"title":"Connecting the dots: Managing species interaction networks to mitigate the impacts of global change.","authors":"Luis Abdala-Roberts, Adriana Puentes, Deborah L Finke, Robert J Marquis, Marta Montserrat, Erik H Poelman, Sergio Rasmann, Arnaud Sentis, Celia C Symons, Nicole M van Dam, Gina Wimp, Christer Björkman, Kailen A Mooney","doi":"10.7554/eLife.98899","DOIUrl":"10.7554/eLife.98899","url":null,"abstract":"Global change is causing unprecedented degradation of the Earth's biological systems and thus undermining human prosperity. Past practices have focused either on monitoring biodiversity decline or mitigating ecosystem services degradation. Missing, but critically needed, are management approaches that monitor and restore species interaction networks, thus bridging existing practices. Our overall aim here is to lay the foundations of a framework for developing network management, defined here as the study, monitoring, and management of species interaction networks. We review theory and empirical evidence demonstrating the importance of species interaction networks for the provisioning of ecosystem services, how human impacts on those networks lead to network rewiring that underlies ecosystem service degradation, and then turn to case studies showing how network management has effectively mitigated such effects or aided in network restoration. We also examine how emerging technologies for data acquisition and analysis are providing new opportunities for monitoring species interactions and discuss the opportunities and challenges of developing effective network management. In summary, we propose that network management provides key mechanistic knowledge on ecosystem degradation that links species- to ecosystem-level responses to global change, and that emerging technological tools offer the opportunity to accelerate its widespread adoption.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FtsK is critical for the assembly of the unique divisome complex of the FtsZ-less Chlamydia trachomatis.

IF 6.4 1区生物学

eLife Pub Date : 2025-04-07 DOI: 10.7554/eLife.104199

McKenna Harpring, Junghoon Lee, Guangming Zhong, Scot P Ouellette, John V Cox

{"title":"FtsK is critical for the assembly of the unique divisome complex of the FtsZ-less Chlamydia trachomatis.","authors":"McKenna Harpring, Junghoon Lee, Guangming Zhong, Scot P Ouellette, John V Cox","doi":"10.7554/eLife.104199","DOIUrl":"10.7554/eLife.104199","url":null,"abstract":"Chlamydia trachomatis serovar L2 (Ct), an obligate intracellular bacterium that does not encode FtsZ, divides by a polarized budding process. In the absence of FtsZ, we show that FtsK, a chromosomal translocase, is critical for divisome assembly in Ct. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge in the next round of division. The divisome in Ct has a hybrid composition, containing elements of the divisome and elongasome from other bacteria, and FtsK is recruited to nascent divisomes prior to the other chlamydial divisome proteins assayed, including the PBP2 and PBP3 transpeptidases, and MreB and MreC. Knocking down FtsK prevents divisome assembly in Ct and inhibits cell division and septal peptidoglycan synthesis. We further show that MreB does not function like FtsZ and serve as a scaffold for the assembly of the Ct divisome. Rather, MreB is one of the last proteins recruited to the chlamydial divisome, and it is necessary for the formation of septal peptidoglycan rings. Our studies illustrate the critical role of chlamydial FtsK in coordinating divisome assembly and peptidoglycan synthesis in this obligate intracellular bacterial pathogen.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0