Nature Reviews Molecular Cell Biology最新文献_第7页

CLASPing and squeezing during cell migration 细胞迁移过程中的 CLASPing 和挤压

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-04 DOI: 10.1038/s41580-024-00779-z

Lisa Heinke

引用次数: 0

Mechanisms of assembly and remodelling of the extracellular matrix 细胞外基质的组装和重塑机制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-02 DOI: 10.1038/s41580-024-00767-3

Alexandra Naba

{"title":"Mechanisms of assembly and remodelling of the extracellular matrix","authors":"Alexandra Naba","doi":"10.1038/s41580-024-00767-3","DOIUrl":"10.1038/s41580-024-00767-3","url":null,"abstract":"The extracellular matrix (ECM) is the complex meshwork of proteins and glycans that forms the scaffold that surrounds and supports cells. It exerts key roles in all aspects of metazoan physiology, from conferring physical and mechanical properties on tissues and organs to modulating cellular processes such as proliferation, differentiation and migration. Understanding the mechanisms that orchestrate the assembly of the ECM scaffold is thus crucial to understand ECM functions in health and disease. This Review discusses novel insights into the compositional diversity of matrisome components and the mechanisms that lead to tissue-specific assemblies and architectures tailored to support specific functions. The Review then highlights recently discovered mechanisms, including post-translational modifications and metabolic pathways such as amino acid availability and the circadian clock, that modulate ECM secretion, assembly and remodelling in homeostasis and human diseases. Last, the Review explores the potential of ‘matritherapies’, that is, strategies to normalize ECM composition and architecture to achieve a therapeutic benefit. The extracellular matrix (ECM) is a scaffold that supports cell structure and function. This Review discusses the compositional diversity, tissue-specific assembly and remodelling of the ECM in health and disease, and explores its potential for therapeutic targeting.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"865-885"},"PeriodicalIF":81.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118118","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

Epigenetic gene regulation in plants and its potential applications in crop improvement 植物表观遗传基因调控及其在作物改良中的潜在应用。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-27 DOI: 10.1038/s41580-024-00769-1

Heng Zhang, Jian-Kang Zhu

{"title":"Epigenetic gene regulation in plants and its potential applications in crop improvement","authors":"Heng Zhang, Jian-Kang Zhu","doi":"10.1038/s41580-024-00769-1","DOIUrl":"10.1038/s41580-024-00769-1","url":null,"abstract":"DNA methylation, also known as 5-methylcytosine, is an epigenetic modification that has crucial functions in plant growth, development and adaptation. The cellular DNA methylation level is tightly regulated by the combined action of DNA methyltransferases and demethylases. Protein complexes involved in the targeting and interpretation of DNA methylation have been identified, revealing intriguing roles of methyl-DNA binding proteins and molecular chaperones. Structural studies and in vitro reconstituted enzymatic systems have provided mechanistic insights into RNA-directed DNA methylation, the main pathway catalysing de novo methylation in plants. A better understanding of the regulatory mechanisms will enable locus-specific manipulation of the DNA methylation status. CRISPR–dCas9-based epigenome editing tools are being developed for this goal. Given that DNA methylation patterns can be stably transmitted through meiosis, and that large phenotypic variations can be contributed by epimutations, epigenome editing holds great promise in crop breeding by creating additional phenotypic variability on the same genetic material. This Review outlines progress in understanding the mechanisms of DNA methylation regulation in plants. Studies in various plants have revealed novel and diverse biological functions of DNA methylation that might assist in developing epigenome editing approaches suitable for crop breeding.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"51-67"},"PeriodicalIF":81.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081023","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

Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics 利用单细胞和空间转录组学分析细胞特征和组织结构

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-21 DOI: 10.1038/s41580-024-00768-2

Gunsagar S. Gulati, Jeremy Philip D’Silva, Yunhe Liu, Linghua Wang, Aaron M. Newman

{"title":"Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics","authors":"Gunsagar S. Gulati, Jeremy Philip D’Silva, Yunhe Liu, Linghua Wang, Aaron M. Newman","doi":"10.1038/s41580-024-00768-2","DOIUrl":"10.1038/s41580-024-00768-2","url":null,"abstract":"Single-cell transcriptomics has broadened our understanding of cellular diversity and gene expression dynamics in healthy and diseased tissues. Recently, spatial transcriptomics has emerged as a tool to contextualize single cells in multicellular neighbourhoods and to identify spatially recurrent phenotypes, or ecotypes. These technologies have generated vast datasets with targeted-transcriptome and whole-transcriptome profiles of hundreds to millions of cells. Such data have provided new insights into developmental hierarchies, cellular plasticity and diverse tissue microenvironments, and spurred a burst of innovation in computational methods for single-cell analysis. In this Review, we discuss recent advancements, ongoing challenges and prospects in identifying and characterizing cell states and multicellular neighbourhoods. We discuss recent progress in sample processing, data integration, identification of subtle cell states, trajectory modelling, deconvolution and spatial analysis. Furthermore, we discuss the increasing application of deep learning, including foundation models, in analysing single-cell and spatial transcriptomics data. Finally, we discuss recent applications of these tools in the fields of stem cell biology, immunology, and tumour biology, and the future of single-cell and spatial transcriptomics in biological research and its translation to the clinic. Single-cell and spatial transcriptomics are transforming our understanding of cell plasticity and tissue diversity. This Review discusses technical and computational advancements and challenges in characterizing cell states and tissues during embryogenesis, tumorigenesis and immune responses, and the application of these tools to the clinic.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"11-31"},"PeriodicalIF":81.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013799","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

Far from the cytoplasmic crowd 远离细胞质人群

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-19 DOI: 10.1038/s41580-024-00774-4

Eytan Zlotorynski

引用次数: 0

Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases 神经退行性疾病中自噬-溶酶体功能障碍的机制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-06 DOI: 10.1038/s41580-024-00757-5

Ralph A. Nixon, David C. Rubinsztein

{"title":"Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases","authors":"Ralph A. Nixon, David C. Rubinsztein","doi":"10.1038/s41580-024-00757-5","DOIUrl":"10.1038/s41580-024-00757-5","url":null,"abstract":"Autophagy is a lysosome-based degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and aggregate-prone proteins. Their postmitotic nature and extremely polarized morphologies make neurons particularly vulnerable to disruptions caused by autophagy–lysosomal defects, especially as the brain ages. Consequently, mutations in genes regulating autophagy and lysosomal functions cause a wide range of neurodegenerative diseases. Here, we review the role of autophagy and lysosomes in neurodegenerative diseases such as Alzheimer disease, Parkinson disease and frontotemporal dementia. We also consider the strong impact of cellular ageing on lysosomes and autophagy as a tipping point for the late-age emergence of related neurodegenerative disorders. Many of these diseases have primary defects in autophagy, for example affecting autophagosome formation, and in lysosomal functions, especially pH regulation and calcium homeostasis. We have aimed to provide an integrative framework for understanding the central importance of autophagic–lysosomal function in neuronal health and disease. The autophagy–lysosome pathway eliminates damaged organelles and aggregation-prone proteins, which is particularly important in neurons, where clearance of such substrates is restricted. Autophagy or lysosome deficiencies, often exacerbated by ageing, impact neuronal function and cause neurodegenerative diseases such as Alzheimer disease or Parkinson disease.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"926-946"},"PeriodicalIF":81.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895188","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

Structural biology and molecular pharmacology of voltage-gated ion channels 电压门控离子通道的结构生物学和分子药理学。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-05 DOI: 10.1038/s41580-024-00763-7

Jian Huang, Xiaojing Pan, Nieng Yan

{"title":"Structural biology and molecular pharmacology of voltage-gated ion channels","authors":"Jian Huang, Xiaojing Pan, Nieng Yan","doi":"10.1038/s41580-024-00763-7","DOIUrl":"10.1038/s41580-024-00763-7","url":null,"abstract":"Voltage-gated ion channels (VGICs), including those for Na+, Ca2+ and K+, selectively permeate ions across the cell membrane in response to changes in membrane potential, thus participating in physiological processes involving electrical signalling, such as neurotransmission, muscle contraction and hormone secretion. Aberrant function or dysregulation of VGICs is associated with a diversity of neurological, psychiatric, cardiovascular and muscular disorders, and approximately 10% of FDA-approved drugs directly target VGICs. Understanding the structure–function relationship of VGICs is crucial for our comprehension of their working mechanisms and role in diseases. In this Review, we discuss how advances in single-particle cryo-electron microscopy have afforded unprecedented structural insights into VGICs, especially on their interactions with clinical and investigational drugs. We present a comprehensive overview of the recent advances in the structural biology of VGICs, with a focus on how prototypical drugs and toxins modulate VGIC activities. We explore how these structures elucidate the molecular basis for drug actions, reveal novel pharmacological sites, and provide critical clues to future drug discovery. Voltage-gated ion channels (VGICs) regulate ion permeability in multiple physiological processes, thereby representing important disease targets. This Review discusses how advances in cryo-electron microscopy have contributed to our understanding of VGIC structures and mechanisms and their interactions with drugs.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"904-925"},"PeriodicalIF":81.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893875","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

MYB-related proteins make chloroplasts 与 MYB 相关的蛋白质使叶绿体

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-02 DOI: 10.1038/s41580-024-00771-7

Kim Baumann

引用次数: 0

What does it take to build a nucleus? 构建原子核需要什么？

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-24 DOI: 10.1038/s41580-024-00766-4

Abigail Buchwalter

引用次数: 0

Regulation of and challenges in targeting NAD+ metabolism 针对 NAD+ 代谢的调节和挑战。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-18 DOI: 10.1038/s41580-024-00752-w

Marie E. Migaud, Mathias Ziegler, Joseph A. Baur

{"title":"Regulation of and challenges in targeting NAD+ metabolism","authors":"Marie E. Migaud, Mathias Ziegler, Joseph A. Baur","doi":"10.1038/s41580-024-00752-w","DOIUrl":"10.1038/s41580-024-00752-w","url":null,"abstract":"Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction–oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+ levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+ levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+ and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+ metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+ supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+ and NADH, and non-canonical NAD+ and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+ levels in humans. Nicotinamide adenine dinucleotide (NAD+) has essential roles in metabolism and can be readily supplemented, potentially to benefit human health. This Review discusses recent insights into the roles of the microbiome and cellular compartments in regulating NAD+ metabolism, and the promise and pitfalls of NAD+ supplementation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"822-840"},"PeriodicalIF":81.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723970","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