eLife最新文献 - Book学术

Bruce suppresses autophagy-regulated caspase activity and wing tissue growth in Drosophila. Bruce抑制果蝇自噬调节的caspase活性和翅膀组织生长。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-19 DOI: 10.7554/eLife.109876

Natsuki Shinoda, Yutaro Hama, Nozomi Hanawa, Masayuki Miura

{"title":"Bruce suppresses autophagy-regulated caspase activity and wing tissue growth in Drosophila.","authors":"Natsuki Shinoda, Yutaro Hama, Nozomi Hanawa, Masayuki Miura","doi":"10.7554/eLife.109876","DOIUrl":"https://doi.org/10.7554/eLife.109876","url":null,"abstract":"Caspases are cysteine-aspartic proteases that mediate both lethal and non-lethal cellular outcomes, including the promotion of tissue growth. However, the mechanisms underlying the differential regulation of these activities remain unclear. We have previously shown that among the two Drosophila executioner caspases, Dcp-1 and Drice, Dcp-1 promotes tissue growth in a non-lethal manner, independent of canonical apoptotic signaling. Herein, we demonstrated that overexpressed Dcp-1, but not Drice, was activated without canonical apoptosome components. TurboID-based proximity labeling revealed distinct proximal proteomes, among which Sirtuin 1, an Atg8a deacetylase, which promotes autophagy, was specifically required for Dcp-1 activation. Autophagy-related genes, including Bcl-2 family members Debcl and Buffy, are required for Dcp-1 activation. Structure-based prediction using AlphaFold3 further identified Bruce, an autophagy-regulated inhibitor of apoptosis, as a Dcp-1-specific regulator acting outside the apoptosome-mediated pathway. Physiologically, Bruce suppresses wing tissue growth. These findings indicate that non-lethal Dcp-1 activity is governed by the autophagy-Bruce axis, enabling distinct non-lethal functions independent of cell death.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223563","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

Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking. Syntaxin11缺乏抑制CRAC通道启动，从而抑制T淋巴细胞的细胞毒性和基因表达，而不依赖于膜运输。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-19 DOI: 10.7554/eLife.111335

Sritama Datta, Abhikarsh Gupta, Kunal M Jagetiya, Resmi Bera, Vikas R Tiwari, Megumi Yamashita, Atharva R Yande, Abdul Rishad, Vishal Malik, Sreejith Raran-Kurussi, Sandra Ammann, Mohammad Shahrooei, Kalyaneswar Mandal, Ramanathan Sowdhamini, Murali Prakriya, Adish Dani, Monika Vig

{"title":"Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking.","authors":"Sritama Datta, Abhikarsh Gupta, Kunal M Jagetiya, Resmi Bera, Vikas R Tiwari, Megumi Yamashita, Atharva R Yande, Abdul Rishad, Vishal Malik, Sreejith Raran-Kurussi, Sandra Ammann, Mohammad Shahrooei, Kalyaneswar Mandal, Ramanathan Sowdhamini, Murali Prakriya, Adish Dani, Monika Vig","doi":"10.7554/eLife.111335","DOIUrl":"10.7554/eLife.111335","url":null,"abstract":"Mutations in Syntaxin11 (STX11), a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer cell cytotoxicity. Here, we show that STX11 directly binds and regulates Orai1, the pore-forming subunit of calcium release-activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cells (NFAT)-dependent gene expression in activated lymphocytes. STX11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression, and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis, as well as interleukin-2 expression, could be reversed by ionomycin in patient T lymphocytes, and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in STX11-depleted cells. Further analyses showed that STX11 'primes' Orai1 for optimal on-site multimeric assembly, which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220027","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

Correction: Cold-inducible RNA-binding protein (CIRBP) adjusts clock-gene expression and REM-sleep recovery following sleep deprivation. 修正：冷诱导rna结合蛋白（CIRBP）调节生物钟基因表达和睡眠剥夺后快速眼动睡眠恢复。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-19 DOI: 10.7554/eLife.113484

Marieke M B Hoekstra, Yann Emmenegger, Jeffrey Hubbard, Paul Franken

引用次数: 0

Individual dopaminergic neurons induce unique, yet overlapping combinations of behavioural modulations, including safety learning, memory retrieval, and acute locomotion. 个体多巴胺能神经元诱导独特的，但重叠的行为调节组合，包括安全学习，记忆检索和急性运动。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.106148

Naoko Toshima, Arman Behrad, Franziska Behnke, Gauri Kaushik, Alice Weiglein, Martin Strauch, Juliane Thoener, Oliver Kobler, Maia Lisandra M Wang, Ayaka Fukushima, Markus Dörr, Michael Schleyer

{"title":"Individual dopaminergic neurons induce unique, yet overlapping combinations of behavioural modulations, including safety learning, memory retrieval, and acute locomotion.","authors":"Naoko Toshima, Arman Behrad, Franziska Behnke, Gauri Kaushik, Alice Weiglein, Martin Strauch, Juliane Thoener, Oliver Kobler, Maia Lisandra M Wang, Ayaka Fukushima, Markus Dörr, Michael Schleyer","doi":"10.7554/eLife.106148","DOIUrl":"10.7554/eLife.106148","url":null,"abstract":"Two evolutionary highly conserved functions of dopamine are to carry 'teaching' signals during associative learning and to control movement. In mammals and humans, these functions are generally thought to be produced by different populations of neurons. Here, we investigated in the larva of Drosophila melanogaster whether both these functions can be induced by the same individual dopaminergic neurons in the central brain. Focusing on the dopaminergic neurons of the DL1 cluster, we asked whether the optogenetic activation of individual neurons established associative punishment and/or safety memories, controlled the retrieval of the established memories, and acutely modulated locomotion. We found that each neuron had a unique yet overlapping set of behavioural effects. Several individual neurons both established a memory and modulated acute locomotion by increasing the animals' bending and decreasing their velocity. Our results demonstrate that individual dopaminergic neurons can fulfil a surprisingly broad range of functions in different behavioural contexts. Given the highly conserved roles of the dopaminergic system across the animal kingdom, this study raises the question whether a similarly diverse functionality can be found also in other animals, including humans.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192184","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

In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons. 体内无病毒谱系追踪和实时成像显示，NeuroD1不会将小胶质细胞重编程为神经元。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.112083

Xiaoyu Li, Yuxin Li, Yue Cao, Niewen Hu, Baozhi Yang, Pei Ouyang, Yuxiao Jin, Shuai Gao, Li Cao, Bo Peng, Yanxia Rao

{"title":"In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons.","authors":"Xiaoyu Li, Yuxin Li, Yue Cao, Niewen Hu, Baozhi Yang, Pei Ouyang, Yuxiao Jin, Shuai Gao, Li Cao, Bo Peng, Yanxia Rao","doi":"10.7554/eLife.112083","DOIUrl":"10.7554/eLife.112083","url":null,"abstract":"In situ glia-to-neuron conversion induced by a single transcription factor is a promising regenerative strategy for treating central nervous system injuries and neurodegenerative diseases. Previous studies reported that NeuroD1 can induce microglia-to-neuron cross-lineage conversion and improve recovery after brain injury. However, these findings remain controversial. To examine the ability of NeuroD1 in inducing microglia-to-neuron conversion, we employed virus-free genetic lineage-tracing systems in mice to specifically induce NeuroD1 expression in microglia and track the cell fate of NeuroD1-expressing cells at multiple timepoints. Meanwhile, we longitudinally monitored NeuroD1-expressing microglia via two-photon imaging and characterized their transcriptional profile by single-cell RNA sequencing. All observations across these methods revealed that NeuroD1-expressing cells retained their microglia identity and cannot convert into neurons, no matter under physiological and injury conditions. Instead, sustained expression of NeuroD1 facilitated microglia apoptosis in vivo. Collectively, our findings provide strong evidence that NeuroD1 alone is not sufficient to induce microglia-to-neuron conversion. This study further highlights the importance of rigorous lineage-tracing and cell fate-mapping strategies for validating in situ glia-to-neuron conversion.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192172","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

Correction: Engineered migrasomes provide a robust and thermally stable vaccination platform. 纠正：工程迁移体提供了一个强大的和热稳定的疫苗接种平台。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.113497

Dongju Wang, Haifang Wang, Wei Wan, Zihui Zhu, Takami Sho, Yi Zheng, Xing Zhang, Longyu Dou, Qiang Ding, Li Yu, Zhihua Liu

引用次数: 0

Correction: Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability. 更正：Mask家族蛋白ANKHD1和ANKRD17调节YAP核的输入和稳定性。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.113290

Clara Sidor, Nerea Borreguero-Munoz, Georgina C Fletcher, Ahmed Elbediwy, Oriane Guillermin, Barry J Thompson

引用次数: 0

Separable downmodulation of meiotic axis protein deposition and DNA break induction at chromosome ends. 染色体末端减数分裂轴蛋白沉积与DNA断裂诱导的可分离下调。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.110189

Adhithi R Raghavan, Kieron May, Vijayalakshmi V Subramanian, Hannah G Blitzblau, Neem J Patel, Jonathan Houseley, Andreas Hochwagen

{"title":"Separable downmodulation of meiotic axis protein deposition and DNA break induction at chromosome ends.","authors":"Adhithi R Raghavan, Kieron May, Vijayalakshmi V Subramanian, Hannah G Blitzblau, Neem J Patel, Jonathan Houseley, Andreas Hochwagen","doi":"10.7554/eLife.110189","DOIUrl":"10.7554/eLife.110189","url":null,"abstract":"In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here, we show that multiple, often chromosome-specific, suppressive mechanisms with differing ranges contribute to the consistently low enrichment of recombination-promoting axis proteins and the downregulation of DNA double-strand breaks (DSBs) within 20 kb of telomeres in Saccharomyces cerevisiae. Suppression of axis proteins is associated with cis-encoded signals and correlates with reduced coding density, although whether this sequence feature actively drives suppression remains to be determined. In addition, axis protein suppression requires the histone methyltransferase Dot1 and the Sir silencing complex. We show that Dot1 suppresses Sir complex activity at least in part independently of its canonical target, H3K79, to downmodulate axis protein deposition near chromosome ends. In parallel, the Sir complex, but not Dot1, suppresses the induction of DSBs at a small number of cryptic hotspots by limiting the openness of promoters, the preferred sites of meiotic DSB formation. Much of the reduced DSB induction near chromosome ends persists in dot1 and sir3 mutants, indicating that additional layers of regulation contribute to the robust reduction of meiotic recombination effectors near chromosome ends.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192153","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

RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in Caenorhabditis elegans. 核糖核酸捕获-序列鉴定了秀丽隐杆线虫在免疫和代谢调节中的前肠和后肠在空间上的不同功能。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-16 DOI: 10.7554/eLife.109237

Chung-Chih Liu, Nicolas Seban, Supriya Srinivasan

{"title":"RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in Caenorhabditis elegans.","authors":"Chung-Chih Liu, Nicolas Seban, Supriya Srinivasan","doi":"10.7554/eLife.109237","DOIUrl":"10.7554/eLife.109237","url":null,"abstract":"The intestine integrates food-derived cues to coordinate organismal physiology, yet the molecular specialization of discrete regions along the intestinal epithelium remains unclear. Here, we generate cell type-specific translatomes of the Caenorhabditis elegans intestine during fasting and refeeding using discrete promoters for the anterior quartet of intestinal cells (INT1) and the remaining eight pairs of intestinal cells (INT2-9). We found that the anterior-most INT1 cells are a translationally distinct intestinal subcompartment that is particularly enriched for immune- and stress response genes. Functional assays using novel INT1-specific genes emerging from this study reveal that these specialized cells play a previously unappreciated role in pathogen avoidance and organismal survival. A second critical function of INT1 cells is their role in sensing and responding to the contents of the gut lumen. We show that luminal pyruvate is the key signal linking bacterial nutrients in the gut to secretion of the gut insulin antagonist INS-7. These findings establish INT1 as sentinel enteroendocrine cells that integrate metabolic and immune cues to couple food status with immune and endocrine responses. Our studies also provide a rich resource for dissecting segment-specific intestinal biology, an overlooked and fertile area for future research.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192115","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

The petal identity gene PhDEF has a major binding and regulatory action in the epidermis. 花瓣同源基因PhDEF在表皮中起主要的结合和调控作用。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-15 DOI: 10.7554/eLife.113154

Emma Désert, Quentin Cavallini-Speisser, Evelyne Duvernois-Berthet, Pierre Chambrier, Patrice Morel, Brice Letcher, Carine Rey, Jeremy Just, Suzanne Rodrigues Bento, Daniel Bouyer, Marie Monniaux

{"title":"The petal identity gene PhDEF has a major binding and regulatory action in the epidermis.","authors":"Emma Désert, Quentin Cavallini-Speisser, Evelyne Duvernois-Berthet, Pierre Chambrier, Patrice Morel, Brice Letcher, Carine Rey, Jeremy Just, Suzanne Rodrigues Bento, Daniel Bouyer, Marie Monniaux","doi":"10.7554/eLife.113154","DOIUrl":"10.7554/eLife.113154","url":null,"abstract":"In flowering plants, floral organ identity is specified by the combinatorial action of homeotic genes. While the role of these genes in the early specification of organ identity is well established, their late function throughout floral organ development and in specific cell types is much less characterized. In particular, since plant organs are structured in clonally independent cell layers, whether and how homeotic identity interacts with cell layer identity is unknown. We have previously identified cell layer-specific mutants for the petal identity gene PhDEF in petunia flowers, resulting in drastically different petal phenotypes whether PhDEF is expressed in the petal epidermis or in the mesophyll. In this study, using a combination of single-cell RNA-Seq and chromatin immunoprecipitation on phdef cell layer-specific mutants, we find that PhDEF regulates a different set of target genes in the petal epidermis and mesophyll, with a major regulatory action in the epidermis. We uncover a high diversity of binding profiles in PhDEF target genes, with a complex combination of layer-specific or non-specific binding sites, and a much more prominent binding of PhDEF in the epidermis than in the mesophyll. Our study highlights that floral homeotic genes like PhDEF can have different regulatory actions in different cell contexts, here different cell layers, demonstrating that cell layer identity indeed influences the regulatory processes underlying homeotic identity.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192097","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