CellPub Date : 2025-01-09DOI: 10.1016/j.cell.2024.11.035
{"title":"Selective excitation of bacteria enables growth suppression without antibiotics","authors":"","doi":"10.1016/j.cell.2024.11.035","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.035","url":null,"abstract":"In a recently published article in Device, Saehyun Kim et al. report that selective excitation of bacteria can inhibit their proliferation in an antib…","PeriodicalId":9656,"journal":{"name":"Cell","volume":"37 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937032","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}
CellPub Date : 2025-01-08DOI: 10.1016/j.cell.2024.11.027
Natalie L. Hauglund, Mie Andersen, Klaudia Tokarska, Tessa Radovanovic, Celia Kjaerby, Frederikke L. Sørensen, Zuzanna Bojarowska, Verena Untiet, Sheyla B. Ballestero, Mie G. Kolmos, Pia Weikop, Hajime Hirase, Maiken Nedergaard
{"title":"Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep","authors":"Natalie L. Hauglund, Mie Andersen, Klaudia Tokarska, Tessa Radovanovic, Celia Kjaerby, Frederikke L. Sørensen, Zuzanna Bojarowska, Verena Untiet, Sheyla B. Ballestero, Mie G. Kolmos, Pia Weikop, Hajime Hirase, Maiken Nedergaard","doi":"10.1016/j.cell.2024.11.027","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.027","url":null,"abstract":"As the brain transitions from wakefulness to sleep, processing of external information diminishes while restorative processes, such as glymphatic removal of waste products, are activated. Yet, it is not known what drives brain clearance during sleep. We here employed an array of technologies and identified tightly synchronized oscillations in norepinephrine, cerebral blood volume, and cerebrospinal fluid (CSF) as the strongest predictors of glymphatic clearance during NREM sleep. Optogenetic stimulation of the locus coeruleus induced anti-correlated changes in vasomotion and CSF signal. Furthermore, stimulation of arterial oscillations enhanced CSF inflow, demonstrating that vasomotion acts as a pump driving CSF into the brain. On the contrary, the sleep aid zolpidem suppressed norepinephrine oscillations and glymphatic flow, highlighting the critical role of norepinephrine-driven vascular dynamics in brain clearance. Thus, the micro-architectural organization of NREM sleep, driven by norepinephrine fluctuations and vascular dynamics, is a key determinant for glymphatic clearance.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"77 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936056","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}
CellPub Date : 2025-01-02DOI: 10.1016/j.cell.2024.11.036
Matthew K. Howard, Nicholas Hoppe, Xi-Ping Huang, Darko Mitrovic, Christian B. Billesbølle, Christian B. Macdonald, Eshan Mehrotra, Patrick Rockefeller Grimes, Donovan D. Trinidad, Lucie Delemotte, Justin G. English, Willow Coyote-Maestas, Aashish Manglik
{"title":"Molecular basis of proton sensing by G protein-coupled receptors","authors":"Matthew K. Howard, Nicholas Hoppe, Xi-Ping Huang, Darko Mitrovic, Christian B. Billesbølle, Christian B. Macdonald, Eshan Mehrotra, Patrick Rockefeller Grimes, Donovan D. Trinidad, Lucie Delemotte, Justin G. English, Willow Coyote-Maestas, Aashish Manglik","doi":"10.1016/j.cell.2024.11.036","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.036","url":null,"abstract":"Three proton-sensing G protein-coupled receptors (GPCRs)—GPR4, GPR65, and GPR68—respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues. Using deep mutational scanning (DMS), we determined the functional importance of every residue in GPR68 activation by generating ∼9,500 mutants and measuring their effects on signaling and surface expression. Constant-pH molecular dynamics simulations provided insights into the conformational landscape and protonation patterns of key residues. This unbiased approach revealed that, unlike other proton-sensitive channels and receptors, no single site is critical for proton recognition. Instead, a network of titratable residues extends from the extracellular surface to the transmembrane region, converging on canonical motifs to activate proton-sensing GPCRs. Our approach integrating structure, simulations, and unbiased functional interrogation provides a framework for understanding GPCR signaling complexity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"92 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912175","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}
{"title":"Evolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4","authors":"Xin Wen, Pan Shang, Haidi Chen, Lulu Guo, Naikang Rong, Xiaoyu Jiang, Xuan Li, Junyan Liu, Gongming Yang, Jiacheng Zhang, Kongkai Zhu, Qingbiao Meng, Xuefei He, Zhihai Wang, Zili Liu, Haoran Cheng, Yilin Zheng, Bifei Zhang, Jiaojiao Pang, Zhaoqian Liu, Jin-Peng Sun","doi":"10.1016/j.cell.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.001","url":null,"abstract":"Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species. By solving 7-cryoelectron microscopy (cryo-EM) structures of <em>Xenopus tropicalis</em> GPR4 (xtGPR4) and <em>Mus musculus</em> GPR4 (mmGPR4) under varying pH conditions, we identified that protonation of H<sup>ECL2-45.47</sup> and H<sup>7.36</sup> enabled polar network establishment and tighter association between the extracellular loop 2 (ECL2) and 7 transmembrane (7TM) domain, as well as a conserved propagating path, which are common mechanisms underlying protonation-induced GPR4 activation across different species. Moreover, protonation of distinct extracellular H<sup>ECL2-45.41</sup> contributed to the more acidic optimal pH range of xtGPR4. Overall, our study revealed common and distinct mechanisms of proton sensing by GPR4, from a structural, functional, and evolutionary perspective.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"6 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912184","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.11.037
Agustin Almoril-Porras, Ana C. Calvo, Longgang Niu, Jonathan Beagan, Malcom Díaz García, Josh D. Hawk, Ahmad Aljobeh, Elias M. Wisdom, Ivy Ren, Zhao-Wen Wang, Daniel A. Colón-Ramos
{"title":"Configuration of electrical synapses filters sensory information to drive behavioral choices","authors":"Agustin Almoril-Porras, Ana C. Calvo, Longgang Niu, Jonathan Beagan, Malcom Díaz García, Josh D. Hawk, Ahmad Aljobeh, Elias M. Wisdom, Ivy Ren, Zhao-Wen Wang, Daniel A. Colón-Ramos","doi":"10.1016/j.cell.2024.11.037","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.037","url":null,"abstract":"Synaptic configurations underpin how the nervous system processes sensory information to produce a behavioral response. This is best understood for chemical synapses, and we know far less about how electrical synaptic configurations modulate sensory information processing and context-specific behaviors. We discovered that innexin 1 (INX-1), a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies underlying thermotaxis behavior in <em>C. elegans</em>. Within this well-defined circuit, INX-1 couples two bilaterally symmetric interneurons to integrate sensory information during migratory behavior across temperature gradients. In <em>inx-1</em> mutants, uncoupled interneurons display increased excitability and responses to subthreshold sensory stimuli due to increased membrane resistance and reduced membrane capacitance, resulting in abnormal responses that extend run durations and trap the animals in context-irrelevant tracking of isotherms. Thus, a conserved configuration of electrical synapses enables differential processing of sensory information to deploy context-specific behavioral strategies.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"178 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905054","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.11.024
Melina Vallbracht, Bianca S. Bodmer, Konstantin Fischer, Jana Makroczyova, Sophie L. Winter, Lisa Wendt, Moritz Wachsmuth-Melm, Thomas Hoenen, Petr Chlanda
{"title":"Nucleocapsid assembly drives Ebola viral factory maturation and dispersion","authors":"Melina Vallbracht, Bianca S. Bodmer, Konstantin Fischer, Jana Makroczyova, Sophie L. Winter, Lisa Wendt, Moritz Wachsmuth-Melm, Thomas Hoenen, Petr Chlanda","doi":"10.1016/j.cell.2024.11.024","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.024","url":null,"abstract":"Replication and genome encapsidation of many negative-sense RNA viruses take place in virus-induced membraneless organelles termed viral factories (VFs). Although liquid properties of VFs are believed to control the transition from genome replication to nucleocapsid (NC) assembly, VF maturation and interactions with the cellular environment remain elusive. Here, we apply <em>in situ</em> cryo-correlative light and electron tomography to follow NC assembly and changes in VF morphology and their liquid properties during Ebola virus infection. We show that viral NCs transition from loosely packed helical assemblies in early VFs to compact cylinders that arrange into highly organized parallel bundles later in infection. Early VFs associate with intermediate filaments and are devoid of other host material but become progressively accessible to cellular components. Our data suggest that this process is coupled to VF solidification, loss of sphericity, and dispersion and promotes cytoplasmic exposure of NCs to facilitate their transport to budding sites.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"45 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905055","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.11.025
Nils Burger, Melanie J. Mittenbühler, Haopeng Xiao, Sanghee Shin, Shelley M. Wei, Erik K. Henze, Sebastian Schindler, Sepideh Mehravar, David M. Wood, Jonathan J. Petrocelli, Yizhi Sun, Hans-Georg Sprenger, Pedro Latorre-Muro, Amanda L. Smythers, Luiz H.M. Bozi, Narek Darabedian, Yingde Zhu, Hyuk-Soo Seo, Sirano Dhe-Paganon, Jianwei Che, Edward T. Chouchani
{"title":"The human zinc-binding cysteine proteome","authors":"Nils Burger, Melanie J. Mittenbühler, Haopeng Xiao, Sanghee Shin, Shelley M. Wei, Erik K. Henze, Sebastian Schindler, Sepideh Mehravar, David M. Wood, Jonathan J. Petrocelli, Yizhi Sun, Hans-Georg Sprenger, Pedro Latorre-Muro, Amanda L. Smythers, Luiz H.M. Bozi, Narek Darabedian, Yingde Zhu, Hyuk-Soo Seo, Sirano Dhe-Paganon, Jianwei Che, Edward T. Chouchani","doi":"10.1016/j.cell.2024.11.025","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.025","url":null,"abstract":"Zinc is an essential micronutrient that regulates a wide range of physiological processes, most often through zinc binding to protein cysteine residues. Despite being critical for modulation of protein function, the cysteine sites in the majority of the human proteome that are subject to zinc binding remain undefined. Here, we develop ZnCPT, a deep and quantitative mapping of the zinc-binding cysteine proteome. We define 6,173 zinc-binding cysteines, uncovering protein families across major domains of biology that are subject to constitutive or inducible zinc binding. ZnCPT enables systematic discovery of zinc-regulated structural, enzymatic, and allosteric functional domains. On this basis, we identify 52 cancer genetic dependencies subject to zinc binding and nominate malignancies sensitive to zinc-induced cytotoxicity. We discover a mechanism of zinc regulation over glutathione reductase (GSR), which drives cell death in GSR-dependent lung cancers. We provide ZnCPT as a resource for understanding mechanisms of zinc regulation of protein function.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"182 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905119","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.10.050
Xuan Zhang, Ziliang Luo, Alexandre P. Marand, Haidong Yan, Hosung Jang, Sohyun Bang, John P. Mendieta, Mark A.A. Minow, Robert J. Schmitz
{"title":"A spatially resolved multi-omic single-cell atlas of soybean development","authors":"Xuan Zhang, Ziliang Luo, Alexandre P. Marand, Haidong Yan, Hosung Jang, Sohyun Bang, John P. Mendieta, Mark A.A. Minow, Robert J. Schmitz","doi":"10.1016/j.cell.2024.10.050","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.050","url":null,"abstract":"<em>Cis</em>-regulatory elements (CREs) precisely control spatiotemporal gene expression in cells. Using a spatially resolved single-cell atlas of gene expression with chromatin accessibility across ten soybean tissues, we identified 103 distinct cell types and 303,199 accessible chromatin regions (ACRs). Nearly 40% of the ACRs showed cell-type-specific patterns and were enriched for transcription factor (TF) motifs defining diverse cell identities. We identified <em>de novo</em> enriched TF motifs and explored the conservation of gene regulatory networks underpinning legume symbiotic nitrogen fixation. With comprehensive developmental trajectories for endosperm and embryo, we uncovered the functional transition of the three sub-cell types of endosperm, identified 13 sucrose transporters sharing the DNA binding with one finger 11 (DOF11) motif that were co-upregulated in late peripheral endosperm, and identified key embryo cell-type specification regulators during embryogenesis, including a homeobox TF that promotes cotyledon parenchyma identity. This resource provides a valuable foundation for analyzing gene regulatory programs in soybean cell types across tissues and life stages.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"37 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905057","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.11.028
Marco Y. Hein, Duo Peng, Verina Todorova, Frank McCarthy, Kibeom Kim, Chad Liu, Laura Savy, Camille Januel, Rodrigo Baltazar-Nunez, Madhurya Sekhar, Shivanshi Vaid, Sophie Bax, Madhuri Vangipuram, James Burgess, Leila Njoya, Eileen Wang, Ivan E. Ivanov, Janie R. Byrum, Soorya Pradeep, Carlos G. Gonzalez, Manuel D. Leonetti
{"title":"Global organelle profiling reveals subcellular localization and remodeling at proteome scale","authors":"Marco Y. Hein, Duo Peng, Verina Todorova, Frank McCarthy, Kibeom Kim, Chad Liu, Laura Savy, Camille Januel, Rodrigo Baltazar-Nunez, Madhurya Sekhar, Shivanshi Vaid, Sophie Bax, Madhuri Vangipuram, James Burgess, Leila Njoya, Eileen Wang, Ivan E. Ivanov, Janie R. Byrum, Soorya Pradeep, Carlos G. Gonzalez, Manuel D. Leonetti","doi":"10.1016/j.cell.2024.11.028","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.028","url":null,"abstract":"Defining the subcellular distribution of all human proteins and their remodeling across cellular states remains a central goal in cell biology. Here, we present a high-resolution strategy to map subcellular organization using organelle immunocapture coupled to mass spectrometry. We apply this workflow to a cell-wide collection of membranous and membraneless compartments. A graph-based analysis assigns the subcellular localization of over 7,600 proteins, defines spatial networks, and uncovers interconnections between cellular compartments. Our approach can be deployed to comprehensively profile proteome remodeling during cellular perturbation. By characterizing the cellular landscape following HCoV-OC43 viral infection, we discover that many proteins are regulated by changes in their spatial distribution rather than by changes in abundance. Our results establish that proteome-wide analysis of subcellular remodeling provides key insights for elucidating cellular responses, uncovering an essential role for ferroptosis in OC43 infection. Our dataset can be explored at <span><span>organelles.czbiohub.org</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"26 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905059","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}
CellPub Date : 2024-12-31DOI: 10.1016/j.cell.2024.11.030
Luuk Loeff, Alexander Walter, Gian Tizio Rosalen, Martin Jinek
{"title":"DNA end sensing and cleavage by the Shedu anti-phage defense system","authors":"Luuk Loeff, Alexander Walter, Gian Tizio Rosalen, Martin Jinek","doi":"10.1016/j.cell.2024.11.030","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.030","url":null,"abstract":"The detection of molecular patterns associated with invading pathogens is a hallmark of innate immune systems. Prokaryotes deploy sophisticated host defense mechanisms in innate anti-phage immunity. Shedu is a single-component defense system comprising a putative nuclease SduA. Here, we report cryoelectron microscopy (cryo-EM) structures of apo- and double-stranded DNA (dsDNA)-bound tetrameric SduA assemblies, revealing that the N-terminal domains of SduA form a clamp that recognizes free DNA ends. End binding positions the DNA over the PD-(D/E)XK nuclease domain, resulting in dsDNA nicking at a fixed distance from the 5′ end. The end-directed DNA nicking activity of Shedu prevents propagation of linear DNA <em>in vivo</em>. Finally, we show that phages escape Shedu immunity by suppressing their recombination-dependent DNA replication pathway. Taken together, these results define the antiviral mechanism of Shedu systems, underlining the paradigm that recognition of pathogen-specific nucleic acid structures is a conserved feature of innate immunity across all domains of life.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"147 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905058","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}
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