Nature Cell Biology最新文献_第9页

Gasdermins as evolutionarily conserved executors of inflammation and cell death Gasdermins 作为炎症和细胞死亡的进化保守执行者。

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-26 DOI: 10.1038/s41556-024-01474-z

Kaiwen W. Chen, Petr Broz

{"title":"Gasdermins as evolutionarily conserved executors of inflammation and cell death","authors":"Kaiwen W. Chen, Petr Broz","doi":"10.1038/s41556-024-01474-z","DOIUrl":"10.1038/s41556-024-01474-z","url":null,"abstract":"The gasdermins are a family of pore-forming proteins that have recently emerged as executors of pyroptosis, a lytic form of cell death that is induced by the innate immune system to eradicate infected or malignant cells. Mammalian gasdermins comprise a cytotoxic N-terminal domain, a flexible linker and a C-terminal repressor domain. Proteolytic cleavage in the linker releases the cytotoxic domain, thereby allowing it to form β-barrel membrane pores. Formation of gasdermin pores in the plasma membrane eventually leads to a loss of the electrochemical gradient, cell death and membrane rupture. Here we review recent work that has expanded our understanding of gasdermin biology and function in mammals by revealing their activation mechanism, their regulation and their roles in autoimmunity, host defence and cancer. We further highlight fungal and bacterial gasdermin pore formation pointing to a conserved mechanism of cell death induction. Gasdermins are a family of proteins that form membrane pores and elicit pyroptosis. This Review discusses recent work highlighting their regulation and emerging biological roles, including in non-lethal pore formation and host defence.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1394-1406"},"PeriodicalIF":17.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073302","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

Adaptive microtubule reinforcement enables cell migration through 3D environments 自适应微管强化实现细胞在三维环境中迁移

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-23 DOI: 10.1038/s41556-024-01477-w

引用次数: 0

Exosome regulation by Rubicon in ageing 外泌体在衰老过程中受卢比肯的调控

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-22 DOI: 10.1038/s41556-024-01482-z

Yan Zhen, Harald Stenmark

引用次数: 0

The Rubicon–WIPI axis regulates exosome biogenesis during ageing Rubicon-WIPI轴调节衰老过程中的外泌体生物生成

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-22 DOI: 10.1038/s41556-024-01481-0

Kyosuke Yanagawa, Akiko Kuma, Maho Hamasaki, Shunbun Kita, Tadashi Yamamuro, Kohei Nishino, Shuhei Nakamura, Hiroko Omori, Tatsuya Kaminishi, Satoshi Oikawa, Yoshio Kato, Ryuya Edahiro, Ryosuke Kawagoe, Takako Taniguchi, Yoko Tanaka, Takayuki Shima, Keisuke Tabata, Miki Iwatani, Nao Bekku, Rikinari Hanayama, Yukinori Okada, Takayuki Akimoto, Hidetaka Kosako, Akiko Takahashi, Iichiro Shimomura, Yasushi Sakata, Tamotsu Yoshimori

{"title":"The Rubicon–WIPI axis regulates exosome biogenesis during ageing","authors":"Kyosuke Yanagawa, Akiko Kuma, Maho Hamasaki, Shunbun Kita, Tadashi Yamamuro, Kohei Nishino, Shuhei Nakamura, Hiroko Omori, Tatsuya Kaminishi, Satoshi Oikawa, Yoshio Kato, Ryuya Edahiro, Ryosuke Kawagoe, Takako Taniguchi, Yoko Tanaka, Takayuki Shima, Keisuke Tabata, Miki Iwatani, Nao Bekku, Rikinari Hanayama, Yukinori Okada, Takayuki Akimoto, Hidetaka Kosako, Akiko Takahashi, Iichiro Shimomura, Yasushi Sakata, Tamotsu Yoshimori","doi":"10.1038/s41556-024-01481-0","DOIUrl":"10.1038/s41556-024-01481-0","url":null,"abstract":"Cells release intraluminal vesicles in multivesicular bodies as exosomes to communicate with other cells. Although recent studies suggest an intimate link between exosome biogenesis and autophagy, the detailed mechanism is not fully understood. Here we employed comprehensive RNA interference screening for autophagy-related factors and discovered that Rubicon, a negative regulator of autophagy, is essential for exosome release. Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Interactome analysis of WIPI2d identified the ESCRT components that are required for intraluminal vesicle formation. Notably, we found that Rubicon is required for an age-dependent increase of exosome release in mice. In addition, small RNA sequencing of serum exosomes revealed that Rubicon determines the fate of exosomal microRNAs associated with cellular senescence and longevity pathways. Taken together, our current results suggest that the Rubicon–WIPI axis functions as a key regulator of exosome biogenesis and is responsible for age-dependent changes in exosome quantity and quality. Yanagawa et al. show that the autophagy-related protein Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Rubicon promotes both an increase in exosome release during ageing and the pro-senescent effects of these exosomes.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1558-1570"},"PeriodicalIF":17.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021888","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

RNA sequestration in P-bodies sustains myeloid leukaemia P 型体中的 RNA 封存使髓性白血病得以持续

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-21 DOI: 10.1038/s41556-024-01489-6

Srikanth Kodali, Ludovica Proietti, Gemma Valcarcel, Anna V. López-Rubio, Patrizia Pessina, Thomas Eder, Junchao Shi, Annie Jen, Núria Lupión-Garcia, Anne C. Starner, Mason D. Bartels, Yingzhi Cui, Caroline M. Sands, Ainoa Planas-Riverola, Alba Martínez, Talia Velasco-Hernandez, Laureano Tomás-Daza, Bernhard Alber, Gabriele Manhart, Isabella Maria Mayer, Karoline Kollmann, Alessandro Fatica, Pablo Menendez, Evgenia Shishkova, Rachel E. Rau, Biola M. Javierre, Joshua Coon, Qi Chen, Eric L. Van Nostrand, Jose L. Sardina, Florian Grebien, Bruno Di Stefano

{"title":"RNA sequestration in P-bodies sustains myeloid leukaemia","authors":"Srikanth Kodali, Ludovica Proietti, Gemma Valcarcel, Anna V. López-Rubio, Patrizia Pessina, Thomas Eder, Junchao Shi, Annie Jen, Núria Lupión-Garcia, Anne C. Starner, Mason D. Bartels, Yingzhi Cui, Caroline M. Sands, Ainoa Planas-Riverola, Alba Martínez, Talia Velasco-Hernandez, Laureano Tomás-Daza, Bernhard Alber, Gabriele Manhart, Isabella Maria Mayer, Karoline Kollmann, Alessandro Fatica, Pablo Menendez, Evgenia Shishkova, Rachel E. Rau, Biola M. Javierre, Joshua Coon, Qi Chen, Eric L. Van Nostrand, Jose L. Sardina, Florian Grebien, Bruno Di Stefano","doi":"10.1038/s41556-024-01489-6","DOIUrl":"10.1038/s41556-024-01489-6","url":null,"abstract":"Post-transcriptional mechanisms are fundamental safeguards of progenitor cell identity and are often dysregulated in cancer. Here, we identified regulators of P-bodies as crucial vulnerabilities in acute myeloid leukaemia (AML) through genome-wide CRISPR screens in normal and malignant haematopoietic progenitors. We found that leukaemia cells harbour aberrantly elevated numbers of P-bodies and show that P-body assembly is crucial for initiation and maintenance of AML. Notably, P-body loss had little effect upon homoeostatic haematopoiesis but impacted regenerative haematopoiesis. Molecular characterization of P-bodies purified from human AML cells unveiled their critical role in sequestering messenger RNAs encoding potent tumour suppressors from the translational machinery. P-body dissolution promoted translation of these mRNAs, which in turn rewired gene expression and chromatin architecture in leukaemia cells. Collectively, our findings highlight the contrasting and unique roles of RNA sequestration in P-bodies during tissue homoeostasis and oncogenesis. These insights open potential avenues for understanding myeloid leukaemia and future therapeutic interventions. Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1745-1758"},"PeriodicalIF":17.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013807","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

Retinoic acid induces human gastruloids with posterior embryo-like structures 视黄酸诱导具有后胚胎样结构的人类胃体

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-20 DOI: 10.1038/s41556-024-01487-8

Nobuhiko Hamazaki, Wei Yang, Connor A. Kubo, Chengxiang Qiu, Beth K. Martin, Riddhiman K. Garge, Samuel G. Regalado, Eva K. Nichols, Sriram Pendyala, Nicholas Bradley, Douglas M. Fowler, Choli Lee, Riza M. Daza, Sanjay Srivatsan, Jay Shendure

{"title":"Retinoic acid induces human gastruloids with posterior embryo-like structures","authors":"Nobuhiko Hamazaki, Wei Yang, Connor A. Kubo, Chengxiang Qiu, Beth K. Martin, Riddhiman K. Garge, Samuel G. Regalado, Eva K. Nichols, Sriram Pendyala, Nicholas Bradley, Douglas M. Fowler, Choli Lee, Riza M. Daza, Sanjay Srivatsan, Jay Shendure","doi":"10.1038/s41556-024-01487-8","DOIUrl":"10.1038/s41556-024-01487-8","url":null,"abstract":"Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites and diverse cell types, including neural crest, neural progenitors, renal progenitors and myocytes. Through in silico staging based on single-cell RNA sequencing, we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis. Hamazaki, Yang et al. report that an early pulse of retinoic acid robustly induces human gastruloids with a neural tube, segmented somites and more advanced cell types than conventional gastruloids.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1790-1803"},"PeriodicalIF":17.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01487-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007482","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

Compression-dependent microtubule reinforcement enables cells to navigate confined environments 依赖压缩的微管强化使细胞能够在密闭环境中航行

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-19 DOI: 10.1038/s41556-024-01476-x

Robert J. Ju, Alistair D. Falconer, Christanny J. Schmidt, Marco A. Enriquez Martinez, Kevin M. Dean, Reto P. Fiolka, David P. Sester, Max Nobis, Paul Timpson, Alexis J. Lomakin, Gaudenz Danuser, Melanie D. White, Nikolas K. Haass, Dietmar B. Oelz, Samantha J. Stehbens

{"title":"Compression-dependent microtubule reinforcement enables cells to navigate confined environments","authors":"Robert J. Ju, Alistair D. Falconer, Christanny J. Schmidt, Marco A. Enriquez Martinez, Kevin M. Dean, Reto P. Fiolka, David P. Sester, Max Nobis, Paul Timpson, Alexis J. Lomakin, Gaudenz Danuser, Melanie D. White, Nikolas K. Haass, Dietmar B. Oelz, Samantha J. Stehbens","doi":"10.1038/s41556-024-01476-x","DOIUrl":"10.1038/s41556-024-01476-x","url":null,"abstract":"Cells migrating through complex three-dimensional environments experience considerable physical challenges, including tensile stress and compression. To move, cells need to resist these forces while also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in three dimensions is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of cytoplasmic linker-associated proteins, which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organize contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a role for microtubules as cellular sensors that detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments. Ju et al. show that during three-dimensional cell migration, compression recruits cytoplasmic linker-associated proteins to microtubules; these stabilized microtubules then coordinate nuclear positioning and contractility in confined migration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1520-1534"},"PeriodicalIF":17.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002726","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

Lymphotoxin-β promotes breast cancer bone metastasis colonization and osteolytic outgrowth 淋巴毒素-β促进乳腺癌骨转移瘤的定植和溶骨生长

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-15 DOI: 10.1038/s41556-024-01478-9

Xuxiang Wang, Tengjiang Zhang, Bingxin Zheng, Youxue Lu, Yong Liang, Guoyuan Xu, Luyang Zhao, Yuwei Tao, Qianhui Song, Huiwen You, Haitian Hu, Xuan Li, Keyong Sun, Tianqi Li, Zian Zhang, Jianbin Wang, Xun Lan, Deng Pan, Yang-Xin Fu, Bin Yue, Hanqiu Zheng

{"title":"Lymphotoxin-β promotes breast cancer bone metastasis colonization and osteolytic outgrowth","authors":"Xuxiang Wang, Tengjiang Zhang, Bingxin Zheng, Youxue Lu, Yong Liang, Guoyuan Xu, Luyang Zhao, Yuwei Tao, Qianhui Song, Huiwen You, Haitian Hu, Xuan Li, Keyong Sun, Tianqi Li, Zian Zhang, Jianbin Wang, Xun Lan, Deng Pan, Yang-Xin Fu, Bin Yue, Hanqiu Zheng","doi":"10.1038/s41556-024-01478-9","DOIUrl":"10.1038/s41556-024-01478-9","url":null,"abstract":"Bone metastasis is a lethal consequence of breast cancer. Here we used single-cell transcriptomics to investigate the molecular mechanisms underlying bone metastasis colonization—the rate-limiting step in the metastatic cascade. We identified that lymphotoxin-β (LTβ) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTβ promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTβ activates osteoblasts through nuclear factor-κB2 signalling to secrete CCL2/5, which facilitates tumour cell adhesion to osteoblasts and accelerates osteoclastogenesis, leading to bone metastasis progression. Blocking LTβ signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTβ expression in bone metastases than in primary tumours. Our findings highlight LTβ as a bone niche-induced factor that promotes tumour cell colonization and osteolytic outgrowth and underscore its potential as a therapeutic target for patients with bone metastatic disease. Wang, Zhang, Zheng et al. demonstrate that tumour cell-derived lymphotoxin-β activates NF-κB2 signalling and CCL2/5 secretion in osteoblasts to promote bone metastasis in breast cancer, which may potentially be targeted with a decoy receptor in vivo.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1597-1612"},"PeriodicalIF":17.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986311","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

Docking a flexible basket onto the core of the nuclear pore complex 将柔性篮对接到核孔复合体的核心上

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-13 DOI: 10.1038/s41556-024-01484-x

Edvinas Stankunas, Alwin Köhler

{"title":"Docking a flexible basket onto the core of the nuclear pore complex","authors":"Edvinas Stankunas, Alwin Köhler","doi":"10.1038/s41556-024-01484-x","DOIUrl":"10.1038/s41556-024-01484-x","url":null,"abstract":"The nuclear basket attaches to the nucleoplasmic side of the nuclear pore complex (NPC), coupling transcription to mRNA quality control and export. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome. Yet, how the basket docks onto the NPC core remains unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, we uncovered a membrane-anchored tripartite junction between basket and NPC core. The basket subunit Nup60 harbours three adjacent short linear motifs, which connect Mlp1, a parallel homodimer consisting of coiled-coil segments interrupted by flexible hinges, and the Nup85 subunit of the Y-complex. We reconstituted the Y-complex•Nup60•Mlp1 assembly on a synthetic membrane and validated the protein interfaces in vivo. Here we explain how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity. Stankunas and Köhler define how the nucleoplasmic portion of the nuclear pore complex (NPC), the basket, docks onto the NPC core by integrating AlphaFold-based interaction screens, electron microscopy, and membrane-templated reconstitutions.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1504-1519"},"PeriodicalIF":17.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01484-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141973981","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

A fatty acid switch drives ferroptosis in EMT 脂肪酸开关驱动 EMT 中的铁变态反应

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-08-13 DOI: 10.1038/s41556-024-01483-y

Alina M. Winkelkotte, Almut Schulze

引用次数: 0