Pub Date : 2024-03-21DOI: 10.1038/s41580-024-00724-0
Susanne Bornelöv
The story of a paper that established the concept of codon optimality and its connection with translation efficiency and mRNA decay.
一篇论文的故事，这篇论文确立了密码子最优性的概念及其与翻译效率和 mRNA 衰减之间的联系。
{"title":"A code within the genetic code","authors":"Susanne Bornelöv","doi":"10.1038/s41580-024-00724-0","DOIUrl":"10.1038/s41580-024-00724-0","url":null,"abstract":"The story of a paper that established the concept of codon optimality and its connection with translation efficiency and mRNA decay.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140182872","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 : 2024-03-20DOI: 10.1038/s41580-024-00706-2
Morgan Shine, Jackson Gordon, Leonard Schärfen, Dagmar Zigackova, Lydia Herzel, Karla M. Neugebauer
Many steps of RNA processing occur during transcription by RNA polymerases. Co-transcriptional activities are deemed commonplace in prokaryotes, in which the lack of membrane barriers allows mixing of all gene expression steps, from transcription to translation. In the past decade, an extraordinary level of coordination between transcription and RNA processing has emerged in eukaryotes. In this Review, we discuss recent developments in our understanding of co-transcriptional gene regulation in both eukaryotes and prokaryotes, comparing methodologies and mechanisms, and highlight striking parallels in how RNA polymerases interact with the machineries that act on nascent RNA. The development of RNA sequencing and imaging techniques that detect transient transcription and RNA processing intermediates has facilitated discoveries of transcription coordination with splicing, 3′-end cleavage and dynamic RNA folding and revealed physical contacts between processing machineries and RNA polymerases. Such studies indicate that intron retention in a given nascent transcript can prevent 3′-end cleavage and cause transcriptional readthrough, which is a hallmark of eukaryotic cellular stress responses. We also discuss how coordination between nascent RNA biogenesis and transcription drives fundamental aspects of gene expression in both prokaryotes and eukaryotes. Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.
{"title":"Co-transcriptional gene regulation in eukaryotes and prokaryotes","authors":"Morgan Shine, Jackson Gordon, Leonard Schärfen, Dagmar Zigackova, Lydia Herzel, Karla M. Neugebauer","doi":"10.1038/s41580-024-00706-2","DOIUrl":"10.1038/s41580-024-00706-2","url":null,"abstract":"Many steps of RNA processing occur during transcription by RNA polymerases. Co-transcriptional activities are deemed commonplace in prokaryotes, in which the lack of membrane barriers allows mixing of all gene expression steps, from transcription to translation. In the past decade, an extraordinary level of coordination between transcription and RNA processing has emerged in eukaryotes. In this Review, we discuss recent developments in our understanding of co-transcriptional gene regulation in both eukaryotes and prokaryotes, comparing methodologies and mechanisms, and highlight striking parallels in how RNA polymerases interact with the machineries that act on nascent RNA. The development of RNA sequencing and imaging techniques that detect transient transcription and RNA processing intermediates has facilitated discoveries of transcription coordination with splicing, 3′-end cleavage and dynamic RNA folding and revealed physical contacts between processing machineries and RNA polymerases. Such studies indicate that intron retention in a given nascent transcript can prevent 3′-end cleavage and cause transcriptional readthrough, which is a hallmark of eukaryotic cellular stress responses. We also discuss how coordination between nascent RNA biogenesis and transcription drives fundamental aspects of gene expression in both prokaryotes and eukaryotes. Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175700","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 : 2024-03-13DOI: 10.1038/s41580-024-00721-3
Aleksi Isomursu
In this Tools of the Trade article, Isomursu (Ivaska lab) describes a new method for dynamic micropatterning, which enables investigation of cell adhesion and migration on substrates that mimic different extracellular matrix environments.
在这篇《贸易工具》（Tools of the Trade）文章中，Isomursu（伊瓦斯卡实验室）介绍了一种动态微图案化的新方法，这种方法可以研究细胞在模拟不同细胞外基质环境的基底上的粘附和迁移。
{"title":"Spatiotemporal control over cell–matrix interactions using dynamic micropatterns","authors":"Aleksi Isomursu","doi":"10.1038/s41580-024-00721-3","DOIUrl":"10.1038/s41580-024-00721-3","url":null,"abstract":"In this Tools of the Trade article, Isomursu (Ivaska lab) describes a new method for dynamic micropatterning, which enables investigation of cell adhesion and migration on substrates that mimic different extracellular matrix environments.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120171","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 : 2024-03-08DOI: 10.1038/s41580-024-00720-4
Kim Baumann
In mouse models of acute kidney injury, the outcome — scarless tissue repair versus fibrosis — depends on the activity of the transcription factor SOX9.
在急性肾损伤的小鼠模型中，结果--无疤痕组织修复还是纤维化--取决于转录因子 SOX9 的活性。
{"title":"A SOX9 switch from regeneration to fibrosis","authors":"Kim Baumann","doi":"10.1038/s41580-024-00720-4","DOIUrl":"10.1038/s41580-024-00720-4","url":null,"abstract":"In mouse models of acute kidney injury, the outcome — scarless tissue repair versus fibrosis — depends on the activity of the transcription factor SOX9.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065584","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 : 2024-03-01DOI: 10.1038/s41580-024-00717-z
Eytan Zlotorynski
Harmful activity of the DNA sensor cGAS in the nucleus is suppressed by a dedicated ubiquitylation complex.
DNA 传感器 cGAS 在细胞核中的有害活性受到专用泛素化复合物的抑制。
{"title":"Keeping a low cGAS profile in the nucleus","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00717-z","DOIUrl":"10.1038/s41580-024-00717-z","url":null,"abstract":"Harmful activity of the DNA sensor cGAS in the nucleus is suppressed by a dedicated ubiquitylation complex.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012980","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 : 2024-02-28DOI: 10.1038/s41580-024-00709-z
Yuchuan Miao, Olivier Pourquié
Segmentation is a fundamental feature of the vertebrate body plan. This metameric organization is first implemented by somitogenesis in the early embryo, when paired epithelial blocks called somites are rhythmically formed to flank the neural tube. Recent advances in in vitro models have offered new opportunities to elucidate the mechanisms that underlie somitogenesis. Notably, models derived from human pluripotent stem cells introduced an efficient proxy for studying this process during human development. In this Review, we summarize the current understanding of somitogenesis gained from both in vivo studies and in vitro studies. We deconstruct the spatiotemporal dynamics of somitogenesis into four distinct modules: dynamic events in the presomitic mesoderm, segmental determination, somite anteroposterior polarity patterning, and epithelial morphogenesis. We first focus on the segmentation clock, as well as signalling and metabolic gradients along the tissue, before discussing the clock and wavefront and other models that account for segmental determination. We then detail the molecular and cellular mechanisms of anteroposterior polarity patterning and somite epithelialization. Somite formation, crucial for organization of the segmental pattern of vertebrate embryos, depends on the oscillatory expression of segmentation clock genes. Novel in vitro models of somitogenesis have provided insights into the spatiotemporal dynamics of gene expression, signalling and metabolic gradients that enable somite formation and patterning.
{"title":"Cellular and molecular control of vertebrate somitogenesis","authors":"Yuchuan Miao, Olivier Pourquié","doi":"10.1038/s41580-024-00709-z","DOIUrl":"10.1038/s41580-024-00709-z","url":null,"abstract":"Segmentation is a fundamental feature of the vertebrate body plan. This metameric organization is first implemented by somitogenesis in the early embryo, when paired epithelial blocks called somites are rhythmically formed to flank the neural tube. Recent advances in in vitro models have offered new opportunities to elucidate the mechanisms that underlie somitogenesis. Notably, models derived from human pluripotent stem cells introduced an efficient proxy for studying this process during human development. In this Review, we summarize the current understanding of somitogenesis gained from both in vivo studies and in vitro studies. We deconstruct the spatiotemporal dynamics of somitogenesis into four distinct modules: dynamic events in the presomitic mesoderm, segmental determination, somite anteroposterior polarity patterning, and epithelial morphogenesis. We first focus on the segmentation clock, as well as signalling and metabolic gradients along the tissue, before discussing the clock and wavefront and other models that account for segmental determination. We then detail the molecular and cellular mechanisms of anteroposterior polarity patterning and somite epithelialization. Somite formation, crucial for organization of the segmental pattern of vertebrate embryos, depends on the oscillatory expression of segmentation clock genes. Novel in vitro models of somitogenesis have provided insights into the spatiotemporal dynamics of gene expression, signalling and metabolic gradients that enable somite formation and patterning.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990750","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 : 2024-02-27DOI: 10.1038/s41580-024-00710-6
Jin H. Yang, Anders S. Hansen
The primary regulators of metazoan gene expression are enhancers, originally functionally defined as DNA sequences that can activate transcription at promoters in an orientation-independent and distance-independent manner. Despite being crucial for gene regulation in animals, what mechanisms underlie enhancer selectivity for promoters, and more fundamentally, how enhancers interact with promoters and activate transcription, remain poorly understood. In this Review, we first discuss current models of enhancer–promoter interactions in space and time and how enhancers affect transcription activation. Next, we discuss different mechanisms that mediate enhancer selectivity, including repression, biochemical compatibility and regulation of 3D genome structure. Through 3D polymer simulations, we illustrate how the ability of 3D genome folding mechanisms to mediate enhancer selectivity strongly varies for different enhancer–promoter interaction mechanisms. Finally, we discuss how recent technical advances may provide new insights into mechanisms of enhancer–promoter interactions and how technical biases in methods such as Hi-C and Micro-C and imaging techniques may affect their interpretation. Gene regulation in animals depends chiefly on enhancers, yet the underlying mechanisms are poorly understood. This Review discusses enhancer–promoter interactions and transcription activation, focusing on how enhancer–promoter selectivity is achieved and on recent technical advances that may provide new insights into transcription activation.
增强子是元动物基因表达的主要调控因子，最初在功能上被定义为能以与方向无关和与距离无关的方式激活启动子转录的 DNA 序列。尽管增强子对动物的基因调控至关重要，但人们对增强子对启动子的选择性以及更根本的增强子如何与启动子相互作用并激活转录的机制仍然知之甚少。在这篇综述中，我们首先讨论增强子与启动子在空间和时间上相互作用的现有模型，以及增强子如何影响转录激活。接下来，我们将讨论介导增强子选择性的不同机制，包括抑制、生化相容性和三维基因组结构调控。通过三维聚合物模拟，我们说明了三维基因组折叠机制介导增强子选择性的能力如何因不同的增强子-启动子相互作用机制而强烈不同。最后，我们讨论了最近的技术进步如何为增强子-启动子相互作用机制提供新的见解，以及 Hi-C 和 Micro-C 等方法和成像技术中的技术偏差如何影响其解释。
{"title":"Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation","authors":"Jin H. Yang, Anders S. Hansen","doi":"10.1038/s41580-024-00710-6","DOIUrl":"10.1038/s41580-024-00710-6","url":null,"abstract":"The primary regulators of metazoan gene expression are enhancers, originally functionally defined as DNA sequences that can activate transcription at promoters in an orientation-independent and distance-independent manner. Despite being crucial for gene regulation in animals, what mechanisms underlie enhancer selectivity for promoters, and more fundamentally, how enhancers interact with promoters and activate transcription, remain poorly understood. In this Review, we first discuss current models of enhancer–promoter interactions in space and time and how enhancers affect transcription activation. Next, we discuss different mechanisms that mediate enhancer selectivity, including repression, biochemical compatibility and regulation of 3D genome structure. Through 3D polymer simulations, we illustrate how the ability of 3D genome folding mechanisms to mediate enhancer selectivity strongly varies for different enhancer–promoter interaction mechanisms. Finally, we discuss how recent technical advances may provide new insights into mechanisms of enhancer–promoter interactions and how technical biases in methods such as Hi-C and Micro-C and imaging techniques may affect their interpretation. Gene regulation in animals depends chiefly on enhancers, yet the underlying mechanisms are poorly understood. This Review discusses enhancer–promoter interactions and transcription activation, focusing on how enhancer–promoter selectivity is achieved and on recent technical advances that may provide new insights into transcription activation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983332","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 : 2024-02-21DOI: 10.1038/s41580-024-00714-2
Josiah B. Passmore, Hugo G. J. Damstra
In this Tools of the Trade article, Hugo Damstra and Josiah Passmore (Kapitein Lab) describe GelMap, which introduces a fluorescent reference grid into the workflow of expansion microscopy experiments, thus enabling a visual readout of sample deformation.
{"title":"Intrinsic calibration and deformation mapping for expansion microscopy using GelMap","authors":"Josiah B. Passmore, Hugo G. J. Damstra","doi":"10.1038/s41580-024-00714-2","DOIUrl":"10.1038/s41580-024-00714-2","url":null,"abstract":"In this Tools of the Trade article, Hugo Damstra and Josiah Passmore (Kapitein Lab) describe GelMap, which introduces a fluorescent reference grid into the workflow of expansion microscopy experiments, thus enabling a visual readout of sample deformation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139915835","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 : 2024-02-20DOI: 10.1038/s41580-024-00702-6
Hari Shroff, Ilaria Testa, Florian Jug, Suliana Manley
The proliferation of microscopy methods for live-cell imaging offers many new possibilities for users but can also be challenging to navigate. The prevailing challenge in live-cell fluorescence microscopy is capturing intra-cellular dynamics while preserving cell viability. Computational methods can help to address this challenge and are now shifting the boundaries of what is possible to capture in living systems. In this Review, we discuss these computational methods focusing on artificial intelligence-based approaches that can be layered on top of commonly used existing microscopies as well as hybrid methods that integrate computation and microscope hardware. We specifically discuss how computational approaches can improve the signal-to-noise ratio, spatial resolution, temporal resolution and multi-colour capacity of live-cell imaging. The prevailing challenge in live-cell fluorescence microscopy is capturing intra-cellular dynamics while preserving cell viability. Alongside developments of microscopy hardware, computational methods — especially those based on machine learning — are powerful tools to improve the signal-to-noise ratio, spatial resolution, temporal resolution and multi-colour capacity of live-cell imaging.
{"title":"Live-cell imaging powered by computation","authors":"Hari Shroff, Ilaria Testa, Florian Jug, Suliana Manley","doi":"10.1038/s41580-024-00702-6","DOIUrl":"10.1038/s41580-024-00702-6","url":null,"abstract":"The proliferation of microscopy methods for live-cell imaging offers many new possibilities for users but can also be challenging to navigate. The prevailing challenge in live-cell fluorescence microscopy is capturing intra-cellular dynamics while preserving cell viability. Computational methods can help to address this challenge and are now shifting the boundaries of what is possible to capture in living systems. In this Review, we discuss these computational methods focusing on artificial intelligence-based approaches that can be layered on top of commonly used existing microscopies as well as hybrid methods that integrate computation and microscope hardware. We specifically discuss how computational approaches can improve the signal-to-noise ratio, spatial resolution, temporal resolution and multi-colour capacity of live-cell imaging. The prevailing challenge in live-cell fluorescence microscopy is capturing intra-cellular dynamics while preserving cell viability. Alongside developments of microscopy hardware, computational methods — especially those based on machine learning — are powerful tools to improve the signal-to-noise ratio, spatial resolution, temporal resolution and multi-colour capacity of live-cell imaging.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913072","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 : 2024-02-16DOI: 10.1038/s41580-023-00698-5
Keren I. Hilgendorf, Benjamin R. Myers, Jeremy F. Reiter
Primary cilia are solitary, immotile sensory organelles present on most cells in the body that participate broadly in human health, physiology and disease. Cilia generate a unique environment for signal transduction with tight control of protein, lipid and second messenger concentrations within a relatively small compartment, enabling reception, transmission and integration of biological information. In this Review, we discuss how cilia function as signalling hubs in cell–cell communication using three signalling pathways as examples: ciliary G-protein-coupled receptors (GPCRs), the Hedgehog (Hh) pathway and polycystin ion channels. We review how defects in these ciliary signalling pathways lead to a heterogeneous group of conditions known as ‘ciliopathies’, including metabolic syndromes, birth defects and polycystic kidney disease. Emerging understanding of these pathways’ transduction mechanisms reveals common themes between these cilia-based signalling pathways that may apply to other pathways as well. These mechanistic insights reveal how cilia orchestrate normal and pathophysiological signalling outputs broadly throughout human biology. Cilia are microtubule-based cell projections that provide a unique environment with precise protein, lipid and second messenger concentrations, thereby creating specialized signalling hubs. This Review discusses recent multidisciplinary, mechanistic insights into cilia-based signalling pathways during development and homeostasis.
原生纤毛是存在于人体大多数细胞上的单生、不动的感觉细胞器，广泛参与人体健康、生理和疾病的过程。纤毛为信号转导创造了独特的环境，在一个相对较小的空间内严格控制蛋白质、脂质和第二信使的浓度，从而实现生物信息的接收、传输和整合。在本综述中，我们将以纤毛 G 蛋白偶联受体（GPCR）、刺猬（Hh）通路和多细胞蛋白离子通道这三种信号通路为例，讨论纤毛如何在细胞-细胞通信中发挥信号枢纽的作用。我们回顾了这些纤毛信号通路的缺陷如何导致一组被称为 "纤毛疾病 "的异质性病症，包括代谢综合征、出生缺陷和多囊肾。对这些途径转导机制的新认识揭示了这些基于纤毛的信号途径之间的共同主题，这些主题可能也适用于其他途径。这些机理研究揭示了纤毛如何在整个人类生物学中协调正常和病理生理信号输出。
{"title":"Emerging mechanistic understanding of cilia function in cellular signalling","authors":"Keren I. Hilgendorf, Benjamin R. Myers, Jeremy F. Reiter","doi":"10.1038/s41580-023-00698-5","DOIUrl":"10.1038/s41580-023-00698-5","url":null,"abstract":"Primary cilia are solitary, immotile sensory organelles present on most cells in the body that participate broadly in human health, physiology and disease. Cilia generate a unique environment for signal transduction with tight control of protein, lipid and second messenger concentrations within a relatively small compartment, enabling reception, transmission and integration of biological information. In this Review, we discuss how cilia function as signalling hubs in cell–cell communication using three signalling pathways as examples: ciliary G-protein-coupled receptors (GPCRs), the Hedgehog (Hh) pathway and polycystin ion channels. We review how defects in these ciliary signalling pathways lead to a heterogeneous group of conditions known as ‘ciliopathies’, including metabolic syndromes, birth defects and polycystic kidney disease. Emerging understanding of these pathways’ transduction mechanisms reveals common themes between these cilia-based signalling pathways that may apply to other pathways as well. These mechanistic insights reveal how cilia orchestrate normal and pathophysiological signalling outputs broadly throughout human biology. Cilia are microtubule-based cell projections that provide a unique environment with precise protein, lipid and second messenger concentrations, thereby creating specialized signalling hubs. This Review discusses recent multidisciplinary, mechanistic insights into cilia-based signalling pathways during development and homeostasis.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139745303","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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