Proceedings of the National Academy of Sciences of the United States of America最新文献_第10页

Macrophages release neuraminidase and cleaved calreticulin for programmed cell removal 巨噬细胞释放神经氨酸酶和cleaved calreticulin进行程序性细胞移除

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-21 DOI: 10.1073/pnas.2426644122

Allison Banuelos, Michelle Baez, Allison Zhang, Leyla Yılmaz, William Kasberg, Regan Volk, Nardin Georgeos, Elle Koren-Sedova, Uyen Le, Andrew T. Burden, Kristopher D. Marjon, Jennifer Lippincott-Schwartz, Balyn W. Zaro, Irving L. Weissman

{"title":"Macrophages release neuraminidase and cleaved calreticulin for programmed cell removal","authors":"Allison Banuelos, Michelle Baez, Allison Zhang, Leyla Yılmaz, William Kasberg, Regan Volk, Nardin Georgeos, Elle Koren-Sedova, Uyen Le, Andrew T. Burden, Kristopher D. Marjon, Jennifer Lippincott-Schwartz, Balyn W. Zaro, Irving L. Weissman","doi":"10.1073/pnas.2426644122","DOIUrl":"https://doi.org/10.1073/pnas.2426644122","url":null,"abstract":"Calreticulin (CALR) is primarily an endoplasmic reticulum chaperone protein that also plays a key role in facilitating programmed cell removal (PrCR) by acting as an “eat-me” signal for macrophages, directing their recognition and engulfment of dying, diseased, or unwanted cells. Recent findings have demonstrated that macrophages can transfer their own CALR onto exposed asialoglycans on target cells, marking them for PrCR. Despite the critical role CALR plays in this process, the molecular mechanisms behind its secretion by macrophages and the formation of binding sites on target cells remain unclear. Our findings show that CALR undergoes C-terminal cleavage upon secretion, producing a truncated form that functions as the active eat-me signal detectable on target cells. We identify cathepsins as potential proteases involved in this cleavage process. Furthermore, we demonstrate that macrophages release neuraminidases, which modify the surface of target cells and facilitate CALR binding. These insights reveal a coordinated mechanism through which lipopolysaccharide (LPS)-activated macrophages regulate CALR cleavage and neuraminidase activity to mark target cells for PrCR. How they recognize the cells to be targeted remains unknown.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"77 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A direct computational assessment of vinculin–actin unbinding kinetics reveals catch-bonding behavior 血管蛋白-肌动蛋白解结合动力学的直接计算评估揭示了捕获键行为

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-21 DOI: 10.1073/pnas.2425982122

Willmor J. Peña Ccoa, Fatemah Mukadum, Aubin Ramon, Guillaume Stirnemann, Glen M. Hocky

{"title":"A direct computational assessment of vinculin–actin unbinding kinetics reveals catch-bonding behavior","authors":"Willmor J. Peña Ccoa, Fatemah Mukadum, Aubin Ramon, Guillaume Stirnemann, Glen M. Hocky","doi":"10.1073/pnas.2425982122","DOIUrl":"https://doi.org/10.1073/pnas.2425982122","url":null,"abstract":"Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular mechanotransduction. In this work, we present a comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate the thermodynamic, kinetic, and mechanistic aspects of this phenomenon at physiologically relevant forces. We dissect a catch bond mechanism in which force shifts vinculin between either a weakly or strongly bound state. Our results demonstrate that models for these states have unbinding times consistent with those from single-molecule studies, and suggest that both have some intrinsic catch-bonding behavior. We provide atomistic insight into this behavior, and show how a directional pulling force can promote the strong or weak state. Crucially, our strategy can be extended to measure the difficult-to-capture effects of small mechanical forces on biomolecular systems in general, and those involved in mechanotransduction more specifically.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"62 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction for Garaizar et al., Toward understanding lipid reorganization in RNA lipid nanoparticles in acidic environments. 纠正Garaizar等人，在酸性环境中理解RNA脂质纳米颗粒中的脂质重组。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-21 DOI: 10.1073/pnas.2509443122

引用次数: 0

Correction for Ahituv et al., Starch-rich plant foods 780,000 y ago: Evidence from Acheulian percussive stone tools. 对Ahituv等人的更正，78万年前富含淀粉的植物性食物：来自阿舍利敲击石器的证据。

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 Epub Date: 2025-05-16 DOI: 10.1073/pnas.2508254122

引用次数: 0

Physical exercise activates a PVN-NAc oxytocin circuit to relieve stress-induced depressive-like behaviors. 体育锻炼激活PVN-NAc催产素回路，以缓解压力引起的抑郁样行为。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 DOI: 10.1073/pnas.2503675122

Jie Xia,Yong Zou,Yuqing Cui,Sen Zhang,Konglin Huo,Wenbin Liu,Zhuochun Huang,Qiang Zhang,Zhengtang Qi,Weina Liu

{"title":"Physical exercise activates a PVN-NAc oxytocin circuit to relieve stress-induced depressive-like behaviors.","authors":"Jie Xia,Yong Zou,Yuqing Cui,Sen Zhang,Konglin Huo,Wenbin Liu,Zhuochun Huang,Qiang Zhang,Zhengtang Qi,Weina Liu","doi":"10.1073/pnas.2503675122","DOIUrl":"https://doi.org/10.1073/pnas.2503675122","url":null,"abstract":"Physical exercise is known to reduce depression, but the underlying brain mechanisms remain unclear. Based on a chronic restraint stress model in mice, we showed that 4-wk treadmill exercise profoundly maintained normal neural activity in the nucleus accumbens (NAc), in association with the prevention of depressive-like behaviors. Microarray analysis conducted in the NAc revealed that the oxytocin (OT) receptor displayed the most significant differential expression, implying a crucial involvement of OT signaling in exercise-induced antidepressant effects. In vivo fiber photometry revealed disrupted OT release in the NAc and altered activity of OT neurons in the paraventricular nucleus (PVN) and their projections to the NAc in stressed mice, which were restored by exercise. Moreover, we found that stress-induced depressive-like behaviors were prevented by activation of the PVN-NAc OT circuit. Additional inhibition of the PVN-NAc OT circuit blocked the antidepressant effects of exercise in stressed mice. In summary, our findings reveal a critical role of the PVN-NAc OT circuit in regulating depressive-like behaviors, which is required for the antidepressant effects of exercise. This neural circuit mechanism provides an explanation for brain network adaptations upon exercise and also suggests a promising therapeutic target for depression.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":"e2503675122"},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase separation of RXRγ drives tumor chemoresistance and represents a therapeutic target for small-cell lung cancer. RXRγ相分离驱动肿瘤化疗耐药，是小细胞肺癌的治疗靶点。

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 DOI: 10.1073/pnas.2421199122

Hong Wang,Jie Huang,Zhenhua Zhang,Yana An,Huizi Sun,Jianghe Chen,Weineng Feng,Hao Duan,Yonggao Mou,Yuanxiang Wang,Peiqing Liu,Huihao Zhou,Hong-Wu Chen,Jian Zhang,Xiaoyun Lu,Junjian Wang

{"title":"Phase separation of RXRγ drives tumor chemoresistance and represents a therapeutic target for small-cell lung cancer.","authors":"Hong Wang,Jie Huang,Zhenhua Zhang,Yana An,Huizi Sun,Jianghe Chen,Weineng Feng,Hao Duan,Yonggao Mou,Yuanxiang Wang,Peiqing Liu,Huihao Zhou,Hong-Wu Chen,Jian Zhang,Xiaoyun Lu,Junjian Wang","doi":"10.1073/pnas.2421199122","DOIUrl":"https://doi.org/10.1073/pnas.2421199122","url":null,"abstract":"Small-cell lung cancer (SCLC) is the most lethal type of lung cancer, characterized by rapid evolution from chemosensitivity to chemoresistance and limited treatment options. However, the mechanisms underlying this evolution remain poorly understood. Here, we show that Retinoid X receptor γ (RXRγ) is uniquely overexpressed in chemo-resistant SCLC tumors, and that RXRγ serves as an essential factor driving chemoresistance in SCLC. RXRγ forms phase-separated droplets with LSD1 in the nucleus, which enhances RXRγ-mediated gene transcription activity and reprograms gene expression, promoting tumor stemness and metastasis, and eventually driving SCLC chemoresistance. In turn, RXRγ antagonist disrupts RXRγ-LSD1 interaction, reducing their binding to the target gene locus, markedly suppressing the expression of the RXRγ target gene network. Finally, RXRγ antagonists strongly suppress tumor growth and metastasis and restore SCLC vulnerability to chemotherapy in multiple preclinical SCLC models, resulting in a substantial extension of survival in mouse models. Thus, these results establish RXRγ as a key player in SCLC by phase separation and as a potential therapeutic target for this deadly disease.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"56 1","pages":"e2421199122"},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Galvanotactic directionality of cell groups depends on group size 细胞群的电流定向取决于细胞群的大小

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 DOI: 10.1073/pnas.2416440122

Calina Copos, Yao-Hui Sun, Kan Zhu, Yan Zhang, Brian Reid, Bruce Draper, Francis Lin, Haicen Yue, Yelena Bernadskaya, Min Zhao, Alex Mogilner

{"title":"Galvanotactic directionality of cell groups depends on group size","authors":"Calina Copos, Yao-Hui Sun, Kan Zhu, Yan Zhang, Brian Reid, Bruce Draper, Francis Lin, Haicen Yue, Yelena Bernadskaya, Min Zhao, Alex Mogilner","doi":"10.1073/pnas.2416440122","DOIUrl":"https://doi.org/10.1073/pnas.2416440122","url":null,"abstract":"Motile cells migrate directionally in the electric field (EF) in a process known as galvanotaxis, an important phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in EFs, that inhibition of PI3 kinase (PI3K) reverses single cells to the anode, and that large cohesive groups of either unperturbed or PI3K-inhibited cells migrate to the cathode. Here, we report that small uninhibited cell groups move to the cathode, while small groups of PI3K-inhibited cells move to the anode. Small groups move faster than large groups, and groups of unperturbed cells move faster than PI3K-inhibited cell groups of comparable sizes. The shapes and sizes of large groups change little when they start migrating, while size and shapes of small groups change significantly, and lamellipodia disappear from the rear edges of these groups. The computational model, according to which cells inside and at the edge of the group interpret directional signals differently, explains the observations. Namely, cells in the group interior are directed to the cathode independently whether they are PI3K-inhibited or not. Meanwhile, the edge cells behave like individual cells: They are directed to the cathode in uninhibited groups and to the anode in PI3K-inhibited groups. As a result, all cells drive uninhibited groups to the cathode, while larger PI3K-inhibited groups are directed by cell majority in the group interior to the cathode, while majority of the edge cells in small groups win the tug-of-war driving these groups to the anode.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"4 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction for Austin et al., Death-receptor activation halts clathrin-dependent endocytosis. 对于Austin等人来说，死亡受体的激活阻止了网格蛋白依赖的内吞作用。

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 Epub Date: 2025-05-15 DOI: 10.1073/pnas.2510913122

引用次数: 0

Structure and evolution of photosystem I in the early-branching cyanobacterium Anthocerotibacter panamensis. 早分枝蓝藻巴拿马Anthocerotibacter panamensis光系统I的结构和进化。

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 Epub Date: 2025-05-14 DOI: 10.1073/pnas.2427090122

Han-Wei Jiang, Christopher J Gisriel, Tanai Cardona, David A Flesher, Gary W Brudvig, Ming-Yang Ho

{"title":"Structure and evolution of photosystem I in the early-branching cyanobacterium Anthocerotibacter panamensis.","authors":"Han-Wei Jiang, Christopher J Gisriel, Tanai Cardona, David A Flesher, Gary W Brudvig, Ming-Yang Ho","doi":"10.1073/pnas.2427090122","DOIUrl":"10.1073/pnas.2427090122","url":null,"abstract":"Thylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis studies in thylakoid-free cyanobacteria were only possible in the model strain Gloeobacter violaceus, limiting our understanding of photosynthesis evolution. Here, we report the isolation, biochemical characterization, cryo-EM structure, and phylogenetic analysis of photosystem I (PSI) from a recently discovered thylakoid-free cyanobacterium, Anthocerotibacter panamensis, a distant relative of the genus Gloeobacter. We find that A. panamensis PSI exhibits a distinct carotenoid composition and has one conserved low-energy chlorophyll site, which was lost in G. violaceus. Furthermore, PSI in thylakoid-free cyanobacteria has changed at the sequence level to a degree comparable to that of other strains, yet its subunit composition and oligomeric form might be identical to that of the most recent common ancestor of cyanobacteria. This study therefore provides a glimpse into the ancient evolution of photosynthesis.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 20","pages":"e2427090122"},"PeriodicalIF":9.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Can AI weather models predict out-of-distribution gray swan tropical cyclones? 人工智能天气模型能预测不分布的灰天鹅热带气旋吗？

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-05-20 DOI: 10.1073/pnas.2420914122

Y. Qiang Sun, Pedram Hassanzadeh, Mohsen Zand, Ashesh Chattopadhyay, Jonathan Weare, Dorian S. Abbot

{"title":"Can AI weather models predict out-of-distribution gray swan tropical cyclones?","authors":"Y. Qiang Sun, Pedram Hassanzadeh, Mohsen Zand, Ashesh Chattopadhyay, Jonathan Weare, Dorian S. Abbot","doi":"10.1073/pnas.2420914122","DOIUrl":"https://doi.org/10.1073/pnas.2420914122","url":null,"abstract":"Predicting gray swan weather extremes, which are possible but so rare that they are absent from the training dataset, is a major concern for AI weather models and long-term climate emulators. An important open question is whether AI models can extrapolate from weaker weather events present in the training set to stronger, unseen weather extremes. To test this, we train independent versions of the AI weather model FourCastNet on the 1979–2015 ERA5 dataset with all data, or with Category 3–5 tropical cyclones (TCs) removed, either globally or only over the North Atlantic or Western Pacific basin. We then test these versions of FourCastNet on 2018–2023 Category 5 TCs (gray swans). All versions yield similar accuracy for global weather, but the one trained without Category 3–5 TCs cannot accurately forecast Category 5 TCs, indicating that these models cannot extrapolate from weaker storms. The versions trained without Category 3–5 TCs in one basin show some skill forecasting Category 5 TCs in that basin, suggesting that FourCastNet can generalize across tropical basins. This is encouraging and surprising because regional information is implicitly encoded in inputs. Given that current state-of-the-art AI weather and climate models have similar learning strategies, we expect our findings to apply to other models. Other types of weather extremes need to be similarly investigated. Our work demonstrates that novel learning strategies are needed for AI models to reliably provide early warning or estimated statistics for the rarest, most impactful TCs, and, possibly, other weather extremes.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"44 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0