Nature Cell Biology最新文献_第10页

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

Mapping the human female reproductive tract 绘制人类女性生殖道图。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-02 DOI: 10.1038/s41556-026-01989-7

Nardhy Gomez-Lopez, Seungbaek Lee

引用次数: 0

Primate neurons with special signalling logic 具有特殊信号逻辑的灵长类神经元。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-02 DOI: 10.1038/s41556-026-01978-w

Roman A. Romanov

引用次数: 0

An atlas of primate insular cortex reveals a signal-processing strategy in von Economo neurons 灵长类动物岛叶皮层图谱揭示了von Economo神经元的信号处理策略。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-02 DOI: 10.1038/s41556-026-02009-4

Rui-Feng Liu, Mengyao Huang, Yuhui Shen, Mingting Shao, Junzhan Jing, Nana Xu, Lei Tang, Biaodi Liu, Jianming Shi, Fanrui Chen, Zhao-Zhe Hao, Xiaolong Jiang, Sheng Liu

{"title":"An atlas of primate insular cortex reveals a signal-processing strategy in von Economo neurons","authors":"Rui-Feng Liu, Mengyao Huang, Yuhui Shen, Mingting Shao, Junzhan Jing, Nana Xu, Lei Tang, Biaodi Liu, Jianming Shi, Fanrui Chen, Zhao-Zhe Hao, Xiaolong Jiang, Sheng Liu","doi":"10.1038/s41556-026-02009-4","DOIUrl":"10.1038/s41556-026-02009-4","url":null,"abstract":"The anterior insular cortex (AIC) is a critical hub integrating exteroceptive and interoceptive information into high-order cognition, yet its neural basis remains incompletely understood. Here, by combining whole-cell-based single-cell transcriptomics with Patch-seq recordings, we resolved and characterized 78 detailed cell types in the macaque AIC, revealing the diversity and specialization of this region in cell type, connectivity profile, signal-processing strategy and metabolic characteristics. Among these, we identified two transcriptomically and morphoelectrically defined von Economo neuron (VEN) subtypes, DSG2-expressing VEN-L and POC5-expressing VEN-S, transcriptomically relating to extratelencephalic and corticothalamic projection neurons, respectively. We also uncovered a previously underappreciated signal-processing strategy by VENs, whereby the geometry of the dendrite-originating axon reshapes action potential dynamics and enhances somatic responsiveness to deep-layer synaptic inputs. Our multimodal atlas establishes a molecular and functional framework for investigating the circuit principles underlying cognitive processes in the primate AIC. Liu, Huang, Shen, Shao, Jing and collaborators combine single-cell transcriptomics with Patch-seq and metabolomics to dissect primate anterior insular cortex. They identify two von Economo neuron (VEN) subtypes and a VEN signal-processing strategy.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 8","pages":"1742-1757"},"PeriodicalIF":22.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02009-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372709","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

Learning from stem cell-based embryo models 学习基于干细胞的胚胎模型。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-01 DOI: 10.1038/s41556-026-02018-3

引用次数: 0

Why the temporal dimension matters in cellular signalling 为什么时间维度在细胞信号传导中很重要。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-06-30 DOI: 10.1038/s41556-026-02006-7

Shuai Yang, Fan Jin

引用次数: 0

Transcription factor condensates as storage 转录因子凝集储存。

IF 22.7 1区生物学