Nature Cell Biology最新文献_第9页

Relative tension shapes embryos 相对张力塑造胚胎

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-13 DOI: 10.1038/s41556-026-02014-7

Evan S. Bardot

引用次数: 0

Cargo capture during ER-phagy er吞噬期间的货物捕获

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-13 DOI: 10.1038/s41556-026-02026-3

Petra Gross

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Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate 解码PRC2在早期胚胎发生中的阶段特异性功能，揭示着床前发育和原始生殖细胞命运的作用。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-10 DOI: 10.1038/s41556-026-02002-x

Chengjie Zhou, Meng Wang, Zhiyuan Chen, Yi Zhang

{"title":"Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate","authors":"Chengjie Zhou, Meng Wang, Zhiyuan Chen, Yi Zhang","doi":"10.1038/s41556-026-02002-x","DOIUrl":"10.1038/s41556-026-02002-x","url":null,"abstract":"Early embryogenesis is accompanied by dynamic epigenetic modifications. Although such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis are less understood. Here, using the dTAG system, we reveal previously underappreciated stage-specific functions of PRC2 in regulating preimplantation and primordial germ cell (PGC) development. We demonstrate that PRC2 plays important roles in regulating maternal-to-zygotic transition and epiblast formation. By systematically analysing H3K27me3 and H3K4me3 dynamics, we redefine the timing of bivalency establishment and uncover a stepwise mechanism governing bivalency acquisition in early embryogenesis. Moreover, PRC2 regulates proper PGC numbers in the epiblast by controlling Esrrb expression in the extraembryonic ectoderm. Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous impact in PGC number regulation, both through interplays between epigenetic–epigenetic and epigenetic–transcription factors networks. Zhou, Wang et al. dissect the role of PRC2 in early embryogenesis through inducible degradation of EED, a core PRC2 subunit, and report that PRC2 is required for proper maternal-to-zygotic transition and promotes epiblast specification.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 8","pages":"1700-1714"},"PeriodicalIF":22.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415959","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

Dynamic control of nucleotide metabolism in physiology and disease 生理和疾病中核苷酸代谢的动态控制。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-08 DOI: 10.1038/s41556-026-02004-9

Dohun Kim, Gerta Hoxhaj

{"title":"Dynamic control of nucleotide metabolism in physiology and disease","authors":"Dohun Kim, Gerta Hoxhaj","doi":"10.1038/s41556-026-02004-9","DOIUrl":"10.1038/s41556-026-02004-9","url":null,"abstract":"Nucleotides are essential for life, serving not only as the building blocks of the genome but also as cellular energy providers, metabolic cofactors and signalling molecules. To sustain cellular function and proliferation, cells must continuously generate, recycle and precisely balance nucleotide pools in response to fluctuating metabolic and environmental demands. Nucleotide metabolism is therefore not a static biosynthetic pathway, but a dynamic system tightly integrated with cell signalling and physiology. Here we highlight the regulatory logic of nucleotide metabolism, from acute post-translational regulation to transcriptional scaling, feedback control and higher-order spatial organization into multi-enzyme assemblies and filaments. Through the lens of human genetic disorders and cancer, we examine how nucleotide depletion, pool imbalance or intermediate toxicity produce striking tissue-selective pathologies. Together, these principles position nucleotide metabolism as a central regulatory axis linking cellular metabolism, signalling and fate in health and disease. This Review discusses the spatial organization of nucleotide metabolism and its integration with cellular signalling pathways, emphasizing its importance as a dynamic regulatory axis in both physiological contexts and disease.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 8","pages":"1640-1655"},"PeriodicalIF":22.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408334","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

Author Correction: In situ cryo-ET defines the ultrastructure of ER exit sites in human cells 作者更正：原位冷冻et定义了人细胞内质网出口位点的超微结构。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-08 DOI: 10.1038/s41556-026-02035-2

Katie W. Downes, Julia R. Flood, Andrea Nans, Sander E. Van der Verren, Anjon Audhya, Giulia Zanetti

引用次数: 0

Addendum: In situ architecture of the human prohibitin complex 附录：人体禁止复合物的原位结构。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-06 DOI: 10.1038/s41556-026-02020-9

Felix Lange, Michael Ratz, Jan-Niklas Dohrke, Maxence Le Vasseur, Dirk Wenzel, Peter Ilgen, Dietmar Riedel, Stefan Jakobs

引用次数: 0

CD44 restricts EGFR mobility to polarize cytoskeletal signalling modules driving bleb-based migration CD44限制EGFR的迁移，使驱动气泡迁移的细胞骨架信号模块极化。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-06 DOI: 10.1038/s41556-026-01981-1

Ankita Jha, Ankit Chandra, Payam E. Farahani, Jared E. Toettcher, Ana M. Pasapera, Jason M. Haugh, Clare M. Waterman

{"title":"CD44 restricts EGFR mobility to polarize cytoskeletal signalling modules driving bleb-based migration","authors":"Ankita Jha, Ankit Chandra, Payam E. Farahani, Jared E. Toettcher, Ana M. Pasapera, Jason M. Haugh, Clare M. Waterman","doi":"10.1038/s41556-026-01981-1","DOIUrl":"10.1038/s41556-026-01981-1","url":null,"abstract":"Cells under high confinement migrate efficiently in low-adhesion environments by forming stable, polarized, hydrostatic pressure-driven leader blebs. Here we investigated the basis of polarized bleb morphology in metastatic melanoma cells migrating under low-adhesive and highly confined microenvironments. Using high-resolution live imaging, molecular perturbations and biosensors, we show that EGF signalling through PI3K stabilizes and maintains polarized leader blebs. EGFR and PI3K activities form a gradient within leader blebs that decreases from rear to front, promoting phosphatidylinositol 3,4,5-trisphosphate and Rac1-GTP accumulation at the bleb rear, whereas phosphatidylinositol 4,5-bisphosphate and RhoA-GTP concentrate at the bleb tip, the inverse of the organization observed in integrin-dependent mesenchymal migration. Optogenetic disruption of this gradient triggers bleb retraction, underscoring its functional importance. Mathematical modelling and experiments identified a mechanism whereby during bleb initiation, CD44 and ERM proteins restrict EGFR mobility within a membrane-apposed cortical actin meshwork at the bleb rear, establishing the EGFR–PI3K–Rac gradient. Together, these findings define the biophysical and molecular mechanisms that underlie polarity in bleb-based migration and highlight how alternative spatial organization of signalling modules supports distinct migration modes in different microenvironments. Jha et al. show that the transmembrane protein CD44 restricts EGFR mobility to maintain an EGFR–PI3K–Rac gradient during bleb-based cell migration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 7","pages":"1408-1423"},"PeriodicalIF":22.7,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-01981-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393394","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

Evolutionarily conserved short linear motifs drive actin filament binding 进化上保守的短线性基序驱动肌动蛋白丝结合。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-06 DOI: 10.1038/s41556-026-01979-9

Themistoklis Paraschiakos, Biao Yuan, Michael Hecht-Bucher, Kostiantyn Sopelniak, Pasquale Cervero, Lisa Simon, Ksenija Zonjic, Dominic Eggers, Franziska Selle, Jing Li, Ali Biabani, Stefan Linder, Thomas C. Marlovits, Sabine Windhorst

{"title":"Evolutionarily conserved short linear motifs drive actin filament binding","authors":"Themistoklis Paraschiakos, Biao Yuan, Michael Hecht-Bucher, Kostiantyn Sopelniak, Pasquale Cervero, Lisa Simon, Ksenija Zonjic, Dominic Eggers, Franziska Selle, Jing Li, Ali Biabani, Stefan Linder, Thomas C. Marlovits, Sabine Windhorst","doi":"10.1038/s41556-026-01979-9","DOIUrl":"10.1038/s41556-026-01979-9","url":null,"abstract":"Regulation of the actin cytoskeleton by actin-binding proteins is essential for cellular homeostasis, and the mode of actin binding determines the activity of actin-binding proteins. Here we identify a ‘short linear actin filament-binding motif’ (SFM) based on the cryo-electron microscopy structure of the ITPKA–actin filament complex. Using the computational pipeline SLiMFold, we discovered 103 human proteins containing SFMs with diverse cellular roles. Phylogenetic analysis suggests that SFMs arose de novo and are conserved across eukaryotes, exhibiting actin filament-binding affinities of 2–12 µM. Critical residues mediating binding and modulating affinity were defined, and the cryo-electron microscopy structures of two SFM–actin filament complexes revealed that SFM binding decreases actin-filament stiffness. These findings indicate that SFMs regulate actin-filament conformation and serve as anchoring modules that connect actin dynamics to a broad variety of cellular functions, providing a framework for understanding the actin-associated roles of numerous proteins. Paraschiakos, Yuan et al., using a computational pipeline, identify the short linear actin filament-binding motif (SFM) as an evolutionarily conserved actin filament-binding motif present in 103 human proteins.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 7","pages":"1437-1452"},"PeriodicalIF":22.7,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-01979-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393393","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

Author Correction: Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance 作者更正：线粒体裂变将ECM机械转导与代谢氧化还原稳态和转移性化疗耐药性联系起来。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-03 DOI: 10.1038/s41556-026-02031-6

Patrizia Romani, Nunzia Nirchio, Mattia Arboit, Vito Barbieri, Anna Tosi, Federica Michielin, Soichi Shibuya, Thomas Benoist, Danchen Wu, Charles Colin Thomas Hindmarch, Monica Giomo, Anna Urciuolo, Flavia Giamogante, Antonella Roveri, Probir Chakravarty, Marco Montagner, Tito Calì, Nicola Elvassore, Stephen L. Archer, Paolo De Coppi, Antonio Rosato, Graziano Martello, Sirio Dupont

引用次数: 0

Cell surface liposome binding (CLiB) allows lipid-binding probe engineering via high-throughput screening 细胞表面脂质体结合（CLiB）允许脂质结合探针工程通过高通量筛选。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-02 DOI: 10.1038/s41556-026-01996-8

Taki Nishimura, Kotaro Tsuboyama, Yuki Nakagaki, Shiou-Ling Lu, Yuki Ishino, Nozomu Kono, Takeshi Noda, Eiji Yamamoto, Noboru Mizushima

{"title":"Cell surface liposome binding (CLiB) allows lipid-binding probe engineering via high-throughput screening","authors":"Taki Nishimura, Kotaro Tsuboyama, Yuki Nakagaki, Shiou-Ling Lu, Yuki Ishino, Nozomu Kono, Takeshi Noda, Eiji Yamamoto, Noboru Mizushima","doi":"10.1038/s41556-026-01996-8","DOIUrl":"10.1038/s41556-026-01996-8","url":null,"abstract":"Lipid-binding domains, traditionally isolated from natural proteins, are essential tools for probing membrane lipid dynamics and specialized cellular compartments. Despite diverse applications, a general strategy for their engineering remains elusive. Here we present a robust and high-throughput method for monitoring protein–lipid interactions, named the cell surface liposome binding (CLiB) assay. Using the assay, we conducted directed evolution of the PX domain from SnxA, isolating high-affinity variants specific for phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Combining the CLiB assay with next-generation sequencing enabled parallel analysis of >6,000 clones, comprehensively identifying key residues critical for lipid binding. An engineered variant, PX-SnxAGV, functioned as a lipid biosensor in yeast and mammalian cells, visualizing PI(3,5)P2-enriched membrane subdomains upon hyperosmotic shock and during microautophagy, thereby suggesting localized PI(3,5)P2 synthesis within spatially restricted regions. This study provides a framework for on-demand generation of lipid-binding probes, facilitating the discovery of membrane compartments characterized by unique lipid compositions. Nishimura et al. develop a platform named cell surface liposome binding (CLiB), which allows the high-throughput monitoring of protein–lipid interactions and can be used to design lipid-binding probes.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 7","pages":"1574-1587"},"PeriodicalIF":22.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372710","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