Science Advances最新文献_第8页

A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.ads7933

Tamanash Bhattacharya, Eva M. Alleman, Tiia S. Freeman, Alexander C. Noyola, Michael Emerman, Harmit S. Malik

{"title":"A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses","authors":"Tamanash Bhattacharya, Eva M. Alleman, Tiia S. Freeman, Alexander C. Noyola, Michael Emerman, Harmit S. Malik","doi":"10.1126/sciadv.ads7933","DOIUrl":"10.1126/sciadv.ads7933","url":null,"abstract":"<div >Most mosquito-transmitted alphaviruses encode a premature opal termination codon upstream of their viral polymerase. We show that the Sindbis virus (SINV) opal codon outperforms other stop codons in primate cells at 37°C due to optimal translational readthrough. However, increased readthrough of all stop codons reduces opal preference at 28°C in primate and mosquito cells. Opal also outperforms all sense codons because opal-to-sense substitutions lead to excess polyprotein production at 37°C, disrupting orderly polyprotein processing and production of viral genomic RNAs (gRNAs) required for virus production. Increased readthrough at 28°C dampens the fitness advantages of opal codons. Unexpectedly, we find that a naturally occurring SINV mutation restores sense-codon fitness by further delaying polyprotein processing, allowing adequate time to produce gRNAs. Similar temperature-dependent mechanisms occur in the distantly related dual-host alphavirus, Ross River virus. Our work highlights sophisticated strategies dual-host alphaviruses use to optimize replication in divergent temperatures through a single codon.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads7933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Broadband localization of light at the termination of a topological photonic waveguide

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adr9569

Daniel Muis, Yandong Li, René Barczyk, Sonakshi Arora, L. Kuipers, Gennady Shvets, Ewold Verhagen

{"title":"Broadband localization of light at the termination of a topological photonic waveguide","authors":"Daniel Muis, Yandong Li, René Barczyk, Sonakshi Arora, L. Kuipers, Gennady Shvets, Ewold Verhagen","doi":"10.1126/sciadv.adr9569","DOIUrl":"10.1126/sciadv.adr9569","url":null,"abstract":"<div >Localized optical field enhancement enables strong light-matter interactions necessary for efficient manipulation and sensing of light. Specifically, tunable broadband energy localization in nanoscale hotspots offers many applications in nanophotonics and quantum optics. We experimentally demonstrate a mechanism for the local enhancement of electromagnetic fields based on strong suppression of backscattering. This is achieved at a designed termination of a topologically nontrivial waveguide that nearly preserves the valley degree of freedom. The symmetry origin of the valley degree of freedom prevents edge states to undergo intervalley scattering at waveguide discontinuities that obey the symmetry of the crystal. Using near-field microscopy, we reveal that this leads to strong confinement of light at the termination of a topological photonic waveguide, even without breaking reciprocity. We emphasize the importance of symmetry conservation by comparing different waveguide termination geometries, confirming that the origin of suppressed backscattering lies with the near conservation of the valley degree of freedom, and show the broad bandwidth of the effect.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr9569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dihydroxyacetone phosphate generated in the chloroplast mediates the activation of TOR by CO2 and light

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adu1240

Manuel J. Mallén-Ponce, Andrea M. Quintero-Moreno, Samuel Gámez-Arcas, Arthur R. Grossman, María Esther Pérez-Pérez, José L. Crespo

{"title":"Dihydroxyacetone phosphate generated in the chloroplast mediates the activation of TOR by CO2 and light","authors":"Manuel J. Mallén-Ponce, Andrea M. Quintero-Moreno, Samuel Gámez-Arcas, Arthur R. Grossman, María Esther Pérez-Pérez, José L. Crespo","doi":"10.1126/sciadv.adu1240","DOIUrl":"10.1126/sciadv.adu1240","url":null,"abstract":"<div >Light and CO<sub>2</sub> assimilation activate the target of rapamycin (TOR) kinase in photosynthetic cells, but how these signals are transmitted to TOR is unknown. Using the green alga <i>Chlamydomonas reinhardtii</i> as a model system, we identified dihydroxyacetone phosphate (DHAP) as the key metabolite regulating TOR in response to carbon and light cues. Metabolomic analyses of synchronized cells revealed that DHAP levels change more than any other metabolite between dark- and light-grown cells and that the addition of the DHAP precursor, dihydroxyacetone (DHA), was sufficient to activate TOR in the dark. We also demonstrated that TOR was insensitive to light or inorganic carbon but not to exogenous DHA in a <i>Chlamydomonas</i> mutant defective in the export of DHAP from the chloroplast. Our results provide a metabolic basis for the mode of TOR control by light and inorganic carbon and indicate that cytoplasmic DHAP is an important metabolic regulator of TOR.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu1240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reciprocal phosphorylation between SOAK1 and SOBIR1 fine-tunes receptor-like protein (RLP)–mediated plant immunity

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adt2315

Yongming Chen, Yingying Song, Zhipeng Tu, Weishuai Bi, Congcong Sun, Tingting Zhao, Xiaodan Wang, Daolong Dou, Guangyuan Xu

{"title":"Reciprocal phosphorylation between SOAK1 and SOBIR1 fine-tunes receptor-like protein (RLP)–mediated plant immunity","authors":"Yongming Chen, Yingying Song, Zhipeng Tu, Weishuai Bi, Congcong Sun, Tingting Zhao, Xiaodan Wang, Daolong Dou, Guangyuan Xu","doi":"10.1126/sciadv.adt2315","DOIUrl":"10.1126/sciadv.adt2315","url":null,"abstract":"<div >SUPPRESSOR OF BIR1-1 (SOBIR1) is a receptor-like kinase (RLK) that acts as a coreceptor for multiple receptor-like proteins (RLPs) to mediate pathogen-associated molecular pattern)–triggered immunity. However, the regulation of SOBIR1 homeostasis and activity remains largely unknown. Our study reveals that SOBIR1-ASSOCIATED PROTEIN KINASE 1 (SOAK1), a member of the receptor-like cytoplasmic kinase (RLCK)-V subfamily with a transmembrane domain, negatively regulates multiple RLP-mediated immune responses. SOAK1 constitutively interacts with SOBIR1 and modulates SOBIR1-dependent immune signaling. SOAK1 directly phosphorylates SOBIR1 at serine-406, substantially impairing its ability to transphosphorylate itself and BAK1. The conservation of serine-406 residue among various flowering plants suggests that phosphorylation at this site plays a critical role in regulating plant immunity. Conversely, SOBIR1 also phosphorylates SOAK1 primarily at serine-73, inhibiting SOAK1’s kinase activity and derepressing SOBIR1 activity. This study elucidates a regulatory mechanism for SOBIR1 activity and highlights an uncharacterized role of RLCK-V subfamily members in plant immunity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt2315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adq0334

Huali Su, Yaogang Zhong, Liqing He, Feng Geng, Xinmin Yin, Yongjun Kou, Cheng-Yao Chiang, Xiaokui Mo, Yunzhou Fan, Yanwei Liu, Qiang Wang, Shino Magaki, Timothy F. Cloughesy, Etienne Lefai, William H Yong, Arnab Chakravarti, Xiang Zhang, Deliang Guo

{"title":"Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth","authors":"Huali Su, Yaogang Zhong, Liqing He, Feng Geng, Xinmin Yin, Yongjun Kou, Cheng-Yao Chiang, Xiaokui Mo, Yunzhou Fan, Yanwei Liu, Qiang Wang, Shino Magaki, Timothy F. Cloughesy, Etienne Lefai, William H Yong, Arnab Chakravarti, Xiang Zhang, Deliang Guo","doi":"10.1126/sciadv.adq0334","DOIUrl":"10.1126/sciadv.adq0334","url":null,"abstract":"<div >Elevated hexosamine biosynthesis fuels tumor growth by facilitating protein and lipid glycosylation. But which enzyme in this pathway is better to serve as an antitumor target remains unclear. Here, we revealed that targeting GFAT1, the rate-limiting enzyme in hexosamine synthesis, exhibits limited inhibitory effects on glioblastoma (GBM), the most lethal brain tumor. This outcome is due to the compensation of NAGK-mediated hexosamine salvage pathway. Unexpectedly, inhibiting PGM3, which controls the flux of both de novo hexosamine synthesis and salvage pathways, down-regulates the expression of other enzymes in this pathway and suppresses SREBP-1, a critical lipogenic transcription factor, effectively inhibiting GBM growth. Unexpectedly, SREBP-1 transcriptionally up-regulates the expression of hexosamine synthesis enzymes, while inhibition of these enzymes in turn down-regulates SREBP-1 activation via reducing N-glycosylation of its transporter, SCAP. Our study identified PGM3 as a promising target for treating GBM. Its inhibition disrupts the SREBP-1 activation-hexosamine synthesis positive feedback regulation to effectively eliminate GBM cells.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq0334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of a high-velocity cloud of the Milky Way as a potential dark galaxy

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.ads4057

Xiao-Lan Liu, Jin-Long Xu, Peng Jiang, Ming Zhu, Chuan-Peng Zhang, Naiping Yu, Ye Xu, Xin Guan, Jun-Jie Wang

{"title":"Discovery of a high-velocity cloud of the Milky Way as a potential dark galaxy","authors":"Xiao-Lan Liu, Jin-Long Xu, Peng Jiang, Ming Zhu, Chuan-Peng Zhang, Naiping Yu, Ye Xu, Xin Guan, Jun-Jie Wang","doi":"10.1126/sciadv.ads4057","DOIUrl":"10.1126/sciadv.ads4057","url":null,"abstract":"<div >High-velocity clouds (HVCs) are composed of neutral hydrogen (H I) moving at velocities that deviate from the general rotational motion of the Milky Way. Now, the origins of the HVCs remain poorly known due to the difficulty in determining their distance and the lack of any other suitable identification. Here we report the detection of a compact gas clump in HVC AC-I, which displays characteristics typical of a disk galaxy, named AC G185.0-11.5, using the H I observations. We estimated the distance of AC G185.0-11.5 to be <span><math><mrow><msubsup><mn>277.7</mn><mrow><mo>−</mo><mn>141.6</mn></mrow><mrow><mo>+</mo><mn>291.3</mn></mrow></msubsup></mrow></math></span> kiloparsecs using the baryonic Tully-Fisher relation and constrained its H I gas mass to be between 3.0 × 10<sup>7</sup> and 4.7 × 10<sup>8</sup> solar masses. The distance determination indicates that the HVC AC-I hosting AC G185.0-11.5 is an extragalactic object in the Local Group. The absence of molecular gas and an optical counterpart for AC G185.0-11.5 implies that it may be a rare dark galaxy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hippocampal perineuronal net degradation identifies prefrontal and striatal circuits involved in schizophrenia-like changes in marmosets

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adu0975

Miriam A. Gwilt, Amy R. Hodgson, Sebastian F. A. Axelsson, Gemma J. Cockcroft, Lauren B. McIver, Matthew Hird, Arkadiusz Stasiak, Colin McKenzie, Samantha H.-Y. Ip, Rudolf N. Cardinal, Stephen J. Sawiak, Selena Milosevic-Sephton, Franklin I. Aigbirhio, Young T. Hong, Timothy D. Fryer, Hannah F. Clarke

{"title":"Hippocampal perineuronal net degradation identifies prefrontal and striatal circuits involved in schizophrenia-like changes in marmosets","authors":"Miriam A. Gwilt, Amy R. Hodgson, Sebastian F. A. Axelsson, Gemma J. Cockcroft, Lauren B. McIver, Matthew Hird, Arkadiusz Stasiak, Colin McKenzie, Samantha H.-Y. Ip, Rudolf N. Cardinal, Stephen J. Sawiak, Selena Milosevic-Sephton, Franklin I. Aigbirhio, Young T. Hong, Timothy D. Fryer, Hannah F. Clarke","doi":"10.1126/sciadv.adu0975","DOIUrl":"10.1126/sciadv.adu0975","url":null,"abstract":"<div >In schizophrenia, anterior hippocampus (aHipp) overactivity is associated with orbitofrontal cortex (OFC) dysfunction, but the contribution to symptomatology is unknown. In rodents, degradation of the hippocampal perineuronal net (PNN) replicates this overactivity, but uncertainty over rodent/human prefrontal homology limits translation to humans. Here, we test the hypothesis that aHipp PNN degradation in a species with a human-like prefrontal cortex, the marmoset, alters aHipp-striatal and aHipp-OFC circuitry. Microdialysis and [<sup>18</sup>F]-fluoro-<span>l</span>-dihydroxyphenylalanine positron emission tomography identified increased dopamine synthesis in the associative striatum, but not the nucleus accumbens, as is seen in schizophrenia, and elevated dopamine and noradrenaline in the OFC. Behaviorally, activity was elevated in a marmoset version of the amphetamine-induced activity test, and impaired probabilistic discrimination learning was seen in an OFC/striatum-dependent task that computational modeling suggests was due to loss of goal-directed behavior. Together, these findings demonstrate that a loss of primate aHipp PNNs is sufficient to induce striatal and prefrontal dysfunction consistent with that observed in humans with schizophrenia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu0975","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Navigating and attributing uncertainty in future tropical cyclone risk estimates

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adn4607

Simona Meiler, Chahan M. Kropf, Jamie W. McCaughey, Chia-Ying Lee, Suzana J. Camargo, Adam H. Sobel, Nadia Bloemendaal, Kerry Emanuel, David N. Bresch

{"title":"Navigating and attributing uncertainty in future tropical cyclone risk estimates","authors":"Simona Meiler, Chahan M. Kropf, Jamie W. McCaughey, Chia-Ying Lee, Suzana J. Camargo, Adam H. Sobel, Nadia Bloemendaal, Kerry Emanuel, David N. Bresch","doi":"10.1126/sciadv.adn4607","DOIUrl":"10.1126/sciadv.adn4607","url":null,"abstract":"<div >Future tropical cyclone risks will evolve with climate change and socioeconomic development, entailing substantial uncertainties. An uncertainty and sensitivity analysis of these risks is vital, yet the chosen model setup influences outcomes. This study investigates how much future tropical cyclone risks are driven by climate and socioeconomic changes, quantifies uncertainty from propagating alternate representations of these systems through the risk modeling chain, and evaluates how strongly each model input contributes to output uncertainty. By comparing these three elements—drivers, uncertainty, and sensitivity—across four distinct tropical cyclone models, we derive findings generalizable beyond individual model setups. We find that average tropical cyclone risk will increase 1 to 5% by 2050 globally, with maximum increases ranging from 10 to 400% by 2100, depending on tropical cyclone model choice, region, and risk model inputs, while the dominant source of uncertainty shifts with modeling choices. Last, we differentiate between aleatory, epistemic, and normative uncertainties, offering guidance to reduce them and inform better decision-making.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adn4607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.adw1489

Maximilian Sichrovsky, Denis Lacabanne, Jonathan J. Ruprecht, Jessica J. Rana, Klaudia Stanik, Mariangela Dionysopoulou, Alice P. Sowton, Martin S. King, Scott A. Jones, Lee Cooper, Steven W. Hardwick, Giulia Paris, Dimitri Y. Chirgadze, Shujing Ding, Ian M. Fearnley, Shane M. Palmer, Els Pardon, Jan Steyaert, Vanessa Leone, Lucy R. Forrest, Sotiria Tavoulari, Edmund R. S. Kunji

{"title":"Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier","authors":"Maximilian Sichrovsky, Denis Lacabanne, Jonathan J. Ruprecht, Jessica J. Rana, Klaudia Stanik, Mariangela Dionysopoulou, Alice P. Sowton, Martin S. King, Scott A. Jones, Lee Cooper, Steven W. Hardwick, Giulia Paris, Dimitri Y. Chirgadze, Shujing Ding, Ian M. Fearnley, Shane M. Palmer, Els Pardon, Jan Steyaert, Vanessa Leone, Lucy R. Forrest, Sotiria Tavoulari, Edmund R. S. Kunji","doi":"10.1126/sciadv.adw1489","DOIUrl":"10.1126/sciadv.adw1489","url":null,"abstract":"<div >The mitochondrial pyruvate carrier transports pyruvate, produced by glycolysis from sugar molecules, into the mitochondrial matrix, as a crucial transport step in eukaryotic energy metabolism. The carrier is a drug target for the treatment of cancers, diabetes mellitus, neurodegeneration, and metabolic dysfunction–associated steatotic liver disease. We have solved the structure of the human MPC1L/MPC2 heterodimer in the inward- and outward-open states by cryo–electron microscopy, revealing its alternating access rocker-switch mechanism. The carrier has a central binding site for pyruvate, which contains an essential lysine and histidine residue, important for its ΔpH-dependent transport mechanism. We have also determined the binding poses of three chemically distinct inhibitor classes, which exploit the same binding site in the outward-open state by mimicking pyruvate interactions and by using aromatic stacking interactions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw1489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-18 DOI: 10.1126/sciadv.ads7627

Huan Wang, Christian Hoffmann, Johannes V. Tromm, Xiao Su, Jordan Elliott, Han Wang, Mengying Deng, Conor McClenaghan, Jean Baum, Zhiping P. Pang, Dragomir Milovanovic, Zheng Shi

{"title":"Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein","authors":"Huan Wang, Christian Hoffmann, Johannes V. Tromm, Xiao Su, Jordan Elliott, Han Wang, Mengying Deng, Conor McClenaghan, Jean Baum, Zhiping P. Pang, Dragomir Milovanovic, Zheng Shi","doi":"10.1126/sciadv.ads7627","DOIUrl":"10.1126/sciadv.ads7627","url":null,"abstract":"<div >Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a substantial challenge. Here, we develop micropipette aspiration and whole-cell patch-clamp (MAPAC), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify multiple molecular factors that distinctly regulate the viscosity, interfacial tension, and maturation of synapsin condensates, confirming the cellular roles of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 16","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads7627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0