Nature Cell Biology最新文献

P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance p4 - atp酶控制磷酸肌苷膜不对称和新霉素耐药性

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-11 DOI: 10.1038/s41556-025-01692-z

Bhawik K. Jain, H. Diessel Duan, Christina Valentine, Ariana Samiha, Huilin Li, Todd R. Graham

{"title":"P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance","authors":"Bhawik K. Jain, H. Diessel Duan, Christina Valentine, Ariana Samiha, Huilin Li, Todd R. Graham","doi":"10.1038/s41556-025-01692-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01692-z","url":null,"abstract":"The aminoglycoside antibiotic neomycin has robust antibacterial properties, yet its clinical utility is curtailed by its nephrotoxicity and ototoxicity. The mechanism by which the polycationic neomycin enters specific eukaryotic cell types remains poorly understood. In budding yeast, NEO1 is required for neomycin resistance and encodes a phospholipid flippase that establishes membrane asymmetry. Here we show that mutations altering Neo1 substrate recognition cause neomycin hypersensitivity by exposing phosphatidylinositol-4-phosphate (PI4P) in the plasma membrane extracellular leaflet. Cryogenic electron microscopy reveals PI4P binding to Neo1 within the substrate translocation pathway. PI4P enters the lumen of the endoplasmic reticulum and is flipped by Neo1 at the Golgi to prevent PI4P secretion to the cell surface. Deficiency of the orthologous ATP9A in human cells also causes exposure of PI4P and neomycin sensitivity. These findings unveil conserved mechanisms of aminoglycoside sensitivity and phosphoinositide homoeostasis, with important implications for signalling by extracellular phosphoinositides.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603106","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

A bridge-like lipid transport protein controls plasma membrane lipid composition and fluidity 桥状脂质转运蛋白控制质膜脂质的组成和流动性

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-11 DOI: 10.1038/s41556-025-01680-3

引用次数: 0

Retrospective and multifactorial single-cell profiling reveals sequential chromatin reorganization during X inactivation 回顾性和多因子单细胞分析揭示了X失活过程中染色质的顺序重组

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-10 DOI: 10.1038/s41556-025-01687-w

Samy Kefalopoulou, Pim M. J. Rullens, Kim L. de Luca, Sandra S. de Vries, Tessy Korthout, Alexander van Oudenaarden, Peter Zeller, Jop Kind

{"title":"Retrospective and multifactorial single-cell profiling reveals sequential chromatin reorganization during X inactivation","authors":"Samy Kefalopoulou, Pim M. J. Rullens, Kim L. de Luca, Sandra S. de Vries, Tessy Korthout, Alexander van Oudenaarden, Peter Zeller, Jop Kind","doi":"10.1038/s41556-025-01687-w","DOIUrl":"https://doi.org/10.1038/s41556-025-01687-w","url":null,"abstract":"The regulation of gene expression is governed at multiple levels of chromatin organization. However, how gene regulation is co-ordinated remains relatively unexplored. Here we develop Dam&ChIC, a method that enables retrospective and multifactorial chromatin profiling in single cells. Dam&ChIC employs chromatin labelling in living cells with m6A to acquire a past chromatin state, coupled with an antibody-mediated readout to capture the present chromatin state. Analyses of diverse factor combinations highlight its versatility and superior resolution. By tracking lamina-associated domain inheritance over the cell cycle, we showcase that Dam&ChIC provides retrospective single-cell chromatin data. When applied in random X chromosome inactivation, Dam&ChIC disentangles the temporal order of chromatin remodelling events. Upon mitotic exit and following Xist expression, the inactive X chromosome undergoes extensive genome–lamina detachment, preceding spreading of Polycomb. We anticipate that Dam&ChIC will be instrumental in unravelling the interconnectivity and order of gene-regulatory events underlying cell-state changes during development.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"153 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594067","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

Never let you go 永远不会让你离开

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-07 DOI: 10.1038/s41556-025-01724-8

Angela R. Parrish

引用次数: 0

An overview of contemporary theories of ageing 当代老龄化理论概述

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-01 DOI: 10.1038/s41556-025-01698-7

João Pedro de Magalhães

引用次数: 0

Emerging connections between myelin and Alzheimer’s disease 髓磷脂与阿尔茨海默病之间的新联系

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-07-01 DOI: 10.1038/s41556-025-01701-1

Anna Bright, Leyla Anne Akay, Joel Blanchard, Li-Huei Tsai

引用次数: 0

The Vps13-like protein BLTP2 regulates phosphatidylethanolamine levels to maintain plasma membrane fluidity and breast cancer aggressiveness vps13样蛋白BLTP2调节磷脂酰乙醇胺水平，维持质膜流动性和乳腺癌侵袭性

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-06-27 DOI: 10.1038/s41556-025-01672-3

Subhrajit Banerjee, Stephan Daetwyler, Xiaofei Bai, Morgane Michaud, Juliette Jouhet, Derk Binns, Shruthi Madhugiri, Emma Johnson, Chao-Wen Wang, Reto Fiolka, Alexandre Toulmay, William A. Prinz

{"title":"The Vps13-like protein BLTP2 regulates phosphatidylethanolamine levels to maintain plasma membrane fluidity and breast cancer aggressiveness","authors":"Subhrajit Banerjee, Stephan Daetwyler, Xiaofei Bai, Morgane Michaud, Juliette Jouhet, Derk Binns, Shruthi Madhugiri, Emma Johnson, Chao-Wen Wang, Reto Fiolka, Alexandre Toulmay, William A. Prinz","doi":"10.1038/s41556-025-01672-3","DOIUrl":"https://doi.org/10.1038/s41556-025-01672-3","url":null,"abstract":"Lipid transport proteins (LTPs) facilitate non-vesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis. A recently identified family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles. One of these, BLTP2, is conserved across species but its function is not known. Here we show that BLTP2 regulates plasma membrane (PM) fluidity by increasing phosphatidylethanolamine (PE) levels in the PM. BLTP2 localizes to endoplasmic reticulum (ER)–PM contact sites, and transports PE in vivo, suggesting it drives PE movement from ER to PM. We find that BLTP2 works in parallel with another pathway that regulates intracellular PE distribution and PM fluidity. BLTP2 expression correlates with breast cancer aggressiveness. We found that BLTP2 facilitates growth of a triple negative breast cancer cell line and sustains its aggressiveness in an in vivo model of metastasis, suggesting maintenance of PM fluidity by BLTP2 may be critical for tumorigenesis in humans.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500446","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

Autophagy-targeted NBR1–p62/SQSTM1 complexes promote breast cancer metastasis by sequestering ITCH 靶向自噬的NBR1-p62 /SQSTM1复合物通过隔离瘙痒促进乳腺癌转移

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-06-27 DOI: 10.1038/s41556-025-01689-8

Gourish Mondal, Hugo Gonzalez, Timothy Marsh, Andrew M. Leidal, Ariadne Vlahakis, Pravin R. Phadatare, Sofı́a Bustamante Eguiguren, Michael Bruck, Akul Naik, Mark Jesus M. Magbanua, Laura A. Huppert, Arun P. Wiita, Jeroen P. Roose, Jennifer M. Rosenbluth, Jayanta Debnath

{"title":"Autophagy-targeted NBR1–p62/SQSTM1 complexes promote breast cancer metastasis by sequestering ITCH","authors":"Gourish Mondal, Hugo Gonzalez, Timothy Marsh, Andrew M. Leidal, Ariadne Vlahakis, Pravin R. Phadatare, Sofı́a Bustamante Eguiguren, Michael Bruck, Akul Naik, Mark Jesus M. Magbanua, Laura A. Huppert, Arun P. Wiita, Jeroen P. Roose, Jennifer M. Rosenbluth, Jayanta Debnath","doi":"10.1038/s41556-025-01689-8","DOIUrl":"https://doi.org/10.1038/s41556-025-01689-8","url":null,"abstract":"Autophagy deficiency in breast cancer promotes metastasis through the accumulation of the autophagy cargo receptor NBR1. Here we show that autophagy normally suppresses breast cancer metastasis by enabling the clearance of NBR1–p62/SQSTM1 complexes that instruct p63-mediated pro-metastatic basal differentiation programmes. When autophagy is inhibited, the autophagy cargo receptors NBR1 and p62/SQSTM1 accumulate within biomolecular condensates in cells, which drives basal differentiation in both mouse and human breast cancer models. Mechanistically, these NBR1–p62/SQSTM1 complexes sequester ITCH, a ubiquitin ligase that degrades and negatively regulates p63 in breast cancer cells, thereby stabilizing and activating p63. Accordingly, mutant forms of NBR1 unable to sequester ITCH into NBR1–p62/SQSTM1 complexes do not promote basal differentiation and metastasis in vivo. Overall, our findings illuminate how proteostatic defects arising in the setting of therapeutic autophagy inhibition modulate epithelial lineage fidelity and metastatic progression.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"50 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500405","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

REM transcription factors and GDE1 shape the DNA methylation landscape through the recruitment of RNA polymerase IV transcription complexes REM转录因子和GDE1通过募集RNA聚合酶IV转录复合物来塑造DNA甲基化景观

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-06-27 DOI: 10.1038/s41556-025-01691-0

Zhongshou Wu, Yan Xue, Shuya Wang, Yuan-Hsin Shih, Zhenhui Zhong, Suhua Feng, Jonathan Draper, Allen Lu, Carsten A. Hoeke, Jihui Sha, Lu Li, James Wohlschlegel, Keqiang Wu, Steven E. Jacobsen

{"title":"REM transcription factors and GDE1 shape the DNA methylation landscape through the recruitment of RNA polymerase IV transcription complexes","authors":"Zhongshou Wu, Yan Xue, Shuya Wang, Yuan-Hsin Shih, Zhenhui Zhong, Suhua Feng, Jonathan Draper, Allen Lu, Carsten A. Hoeke, Jihui Sha, Lu Li, James Wohlschlegel, Keqiang Wu, Steven E. Jacobsen","doi":"10.1038/s41556-025-01691-0","DOIUrl":"https://doi.org/10.1038/s41556-025-01691-0","url":null,"abstract":"In plants, the maintenance of DNA methylation is controlled by several self-reinforcing loops involving histone methylation and non-coding RNAs. However, how methylation is initially patterned at specific genomic loci is largely unknown. Here we describe four Arabidopsis REM transcription factors, VDD, VAL, REM12 and REM13, that recognize specific sequence regions and, together with the protein GENETICS DETERMINES EPIGENETICS1 (GDE1), recruit RNA polymerase IV transcription complexes. This targeted recruitment leads to the production of 24-nucleotide small interfering RNAs that guide DNA methylation to specific genomic sites in plant female reproductive tissues. In the absence of GDE1, polymerase IV transcription complexes are directed to loci bound by an alternative transcription factor, REM8, highlighting the role of REM transcription factors and GDE1 proteins as positional cues for epigenetic modulation. These findings establish a direct connection between sequence-specific transcription factors and the spatial regulation of siRNA production and DNA methylation, offering new insights into the genetic control of epigenetic patterning.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"18 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500407","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

A lysosomal surveillance response to stress extends healthspan 对压力的溶酶体监测反应延长了健康寿命

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-06-26 DOI: 10.1038/s41556-025-01693-y

Terytty Yang Li, Arwen W. Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J. Liu, Rachel N. Arey, Kimberly Morales, Raya B. Liu, Wenzheng Wang, Ang Zhou, Tong-jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H. Houtkooper, Johan Auwerx

{"title":"A lysosomal surveillance response to stress extends healthspan","authors":"Terytty Yang Li, Arwen W. Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J. Liu, Rachel N. Arey, Kimberly Morales, Raya B. Liu, Wenzheng Wang, Ang Zhou, Tong-jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H. Houtkooper, Johan Auwerx","doi":"10.1038/s41556-025-01693-y","DOIUrl":"https://doi.org/10.1038/s41556-025-01693-y","url":null,"abstract":"Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H+-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity and enhanced clearance of protein aggregates in worm models of Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis, thereby improving fitness. The GATA transcription factor ELT-2 governs the LySR programme and its associated beneficial effects. Activating the LySR pathway may therefore represent an attractive mechanism to reduce proteotoxicity and, as such, potentially extend healthspan.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"24 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488383","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