Pub Date : 2024-07-16DOI: 10.1038/s41580-024-00753-9
Celeste Parra Bravo, Sarah A. Naguib, Li Gan
Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions. Tau is a microtubule-binding protein that is expressed primarily in neurons. The abnormal accumulation of tau aggregates in neurons is associated with neurodegenerative diseases, known as tauopathies, such as Alzheimer disease and frontotemporal dementia. This Review discusses recent insights into the diverse cellular functions of tau, the pathology of tau aggregates and the potential for therapeutic interventions.
Tau 蛋白参与了多种细胞过程，包括在神经元中结合和稳定微管的典型作用。Tau病是一种神经退行性疾病，其特征是tau蛋白在神经元中的异常聚集，如额颞叶痴呆症和阿尔茨海默病。tau编码区的突变或破坏tau mRNA剪接的突变、tau翻译后修饰和细胞应激因素（如氧化应激和炎症）会增加tau聚集的倾向并干扰其清除。病理性 tau 与神经退行性疾病的进展密切相关，而 tau 聚集体的扩散与疾病的严重程度有关。最近的技术进步，包括低温电子显微镜和从人类诱导多能干细胞中提取的疾病模型，增加了我们对神经退行性疾病中与 tau 相关的病理的了解。我们在破译 tau 聚集结构以及蛋白质聚集和毒性的分子机制方面取得了重大进展。在这篇综述中，我们将讨论有关 tau 的多种细胞功能和 tau 包涵体病理学的最新见解，并探讨治疗干预措施的潜力。
{"title":"Cellular and pathological functions of tau","authors":"Celeste Parra Bravo, Sarah A. Naguib, Li Gan","doi":"10.1038/s41580-024-00753-9","DOIUrl":"10.1038/s41580-024-00753-9","url":null,"abstract":"Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions. Tau is a microtubule-binding protein that is expressed primarily in neurons. The abnormal accumulation of tau aggregates in neurons is associated with neurodegenerative diseases, known as tauopathies, such as Alzheimer disease and frontotemporal dementia. This Review discusses recent insights into the diverse cellular functions of tau, the pathology of tau aggregates and the potential for therapeutic interventions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"845-864"},"PeriodicalIF":81.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625090","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}
Pub Date : 2024-07-15DOI: 10.1038/s41580-024-00765-5
Paul Nurse
Paul Nurse discusses how a 1971 paper by Culotti and Hartwell inspired him to investigate the cell cycle in fission yeast, and how these genetics studies led to the discovery of cyclin-dependent kinases.
{"title":"The discovery of cyclin-dependent kinases","authors":"Paul Nurse","doi":"10.1038/s41580-024-00765-5","DOIUrl":"10.1038/s41580-024-00765-5","url":null,"abstract":"Paul Nurse discusses how a 1971 paper by Culotti and Hartwell inspired him to investigate the cell cycle in fission yeast, and how these genetics studies led to the discovery of cyclin-dependent kinases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"763-763"},"PeriodicalIF":81.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618206","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}
Pub Date : 2024-07-09DOI: 10.1038/s41580-024-00761-9
Kylie J. Walters
The studies that paved the way for the development of PROTACs (proteolysis-targeting chimeras) as therapeutic strategies, and the HPV vaccine.
这些研究为开发作为治疗策略的 PROTACs（蛋白分解靶向嵌合体）和 HPV 疫苗铺平了道路。
{"title":"Virus–host warfare by PROTACs","authors":"Kylie J. Walters","doi":"10.1038/s41580-024-00761-9","DOIUrl":"10.1038/s41580-024-00761-9","url":null,"abstract":"The studies that paved the way for the development of PROTACs (proteolysis-targeting chimeras) as therapeutic strategies, and the HPV vaccine.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"675-675"},"PeriodicalIF":81.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561352","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}
Pub Date : 2024-07-05DOI: 10.1038/s41580-024-00764-6
Eytan Zlotorynski
Many proteins in the mouse ovary are extremely stable; they enhance proteostasis and limit protein aggregation, thereby supporting the maintenance of the long-lived oocytes.
{"title":"Long-lived proteomes in healthy ovaries","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00764-6","DOIUrl":"10.1038/s41580-024-00764-6","url":null,"abstract":"Many proteins in the mouse ovary are extremely stable; they enhance proteostasis and limit protein aggregation, thereby supporting the maintenance of the long-lived oocytes.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"596-596"},"PeriodicalIF":81.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538245","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}
Pub Date : 2024-07-03DOI: 10.1038/s41580-024-00762-8
Sigurd Braun
An elegant study revealed the distinct roles of different H3K9 methylation states in heterochromatin formation and function.
一项出色的研究揭示了不同的 H3K9 甲基化状态在异染色质形成和功能中的不同作用。
{"title":"Heterochromatin as a balancing act between transcription and gene silencing","authors":"Sigurd Braun","doi":"10.1038/s41580-024-00762-8","DOIUrl":"10.1038/s41580-024-00762-8","url":null,"abstract":"An elegant study revealed the distinct roles of different H3K9 methylation states in heterochromatin formation and function.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"676-676"},"PeriodicalIF":81.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498535","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}
Pub Date : 2024-07-01DOI: 10.1038/s41580-024-00755-7
Kirti Prakash, David Baddeley, Christian Eggeling, Reto Fiolka, Rainer Heintzmann, Suliana Manley, Aleksandra Radenovic, Carlas Smith, Hari Shroff, Lothar Schermelleh
Super-resolution microscopy (SRM) is gaining popularity in biosciences; however, claims about optical resolution are contested and often misleading. In this Viewpoint, experts share their views on resolution and common trade-offs, such as labelling and post-processing, aiming to clarify them for biologists and facilitate deeper understanding and best use of SRM. In this Viewpoint, experts discuss resolution and common trade-offs in super-resolution microscopy, aiming to improve how biologists use the technology.
{"title":"Resolution in super-resolution microscopy — definition, trade-offs and perspectives","authors":"Kirti Prakash, David Baddeley, Christian Eggeling, Reto Fiolka, Rainer Heintzmann, Suliana Manley, Aleksandra Radenovic, Carlas Smith, Hari Shroff, Lothar Schermelleh","doi":"10.1038/s41580-024-00755-7","DOIUrl":"10.1038/s41580-024-00755-7","url":null,"abstract":"Super-resolution microscopy (SRM) is gaining popularity in biosciences; however, claims about optical resolution are contested and often misleading. In this Viewpoint, experts share their views on resolution and common trade-offs, such as labelling and post-processing, aiming to clarify them for biologists and facilitate deeper understanding and best use of SRM. In this Viewpoint, experts discuss resolution and common trade-offs in super-resolution microscopy, aiming to improve how biologists use the technology.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"677-682"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477009","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}
Pub Date : 2024-07-01DOI: 10.1038/s41580-024-00758-4
Tore Skotland, Kim Ekroos, Jeffrey McDonald, Robert Ahrends, Gerhard Liebisch, Kirsten Sandvig
This Comment discusses erroneous reporting of mass spectrometry analyses of lipids in mammalian samples, and provides recommendations for how to avoid it. Publications that report mass spectrometry analyses of lipids often include lipid species that probably do not exist in the samples. Here we provide recommendations for scientists on submitting lipid data, and for reviewers, editors and readers on evaluating these data, to reduce the reporting of erroneous lipid species.
{"title":"Pitfalls in lipid mass spectrometry of mammalian samples — a brief guide for biologists","authors":"Tore Skotland, Kim Ekroos, Jeffrey McDonald, Robert Ahrends, Gerhard Liebisch, Kirsten Sandvig","doi":"10.1038/s41580-024-00758-4","DOIUrl":"10.1038/s41580-024-00758-4","url":null,"abstract":"This Comment discusses erroneous reporting of mass spectrometry analyses of lipids in mammalian samples, and provides recommendations for how to avoid it. Publications that report mass spectrometry analyses of lipids often include lipid species that probably do not exist in the samples. Here we provide recommendations for scientists on submitting lipid data, and for reviewers, editors and readers on evaluating these data, to reduce the reporting of erroneous lipid species.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"759-760"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477007","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}
Pub Date : 2024-07-01DOI: 10.1038/s41580-024-00759-3
Lisa Heinke
In a recent study, Bong et al. identify a polarized distribution of contact sites between the endoplasmic reticulum and plasma membrane in migrating cells, whereby higher density of contacts in the back of the cells prevents the formation of additional migration fronts.
{"title":"Polarized endoplasmic reticulum–plasma membrane contacts in cell migration","authors":"Lisa Heinke","doi":"10.1038/s41580-024-00759-3","DOIUrl":"10.1038/s41580-024-00759-3","url":null,"abstract":"In a recent study, Bong et al. identify a polarized distribution of contact sites between the endoplasmic reticulum and plasma membrane in migrating cells, whereby higher density of contacts in the back of the cells prevents the formation of additional migration fronts.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"595-595"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477008","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}
Pub Date : 2024-06-26DOI: 10.1038/s41580-024-00756-6
Qin Ma, Yi Jiang, Hao Cheng, Dong Xu
Foundation models hold great promise for analyzing single-cell omics data, yet various challenges remain that require further advancements. In this Comment, we discuss the progress, limitations and best practices in applying foundation models to interrogate data and improve downstream tasks in single-cell omics. This Comment discusses the progress, limitations and best practices in applying foundation models to single-cell omics data.
{"title":"Harnessing the deep learning power of foundation models in single-cell omics","authors":"Qin Ma, Yi Jiang, Hao Cheng, Dong Xu","doi":"10.1038/s41580-024-00756-6","DOIUrl":"10.1038/s41580-024-00756-6","url":null,"abstract":"Foundation models hold great promise for analyzing single-cell omics data, yet various challenges remain that require further advancements. In this Comment, we discuss the progress, limitations and best practices in applying foundation models to interrogate data and improve downstream tasks in single-cell omics. This Comment discusses the progress, limitations and best practices in applying foundation models to single-cell omics data.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"593-594"},"PeriodicalIF":81.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458258","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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