Pub Date : 2025-06-23DOI: 10.1038/s41580-025-00864-x
Tito Calì, Emmanuelle M. Bayer, Emily R. Eden, György Hajnóczky, Benoit Kornmann, Laura Lackner, Jen Liou, Karin Reinisch, Hyun-Woo Rhee, Rosario Rizzuto, Luca Scorrano, Marisa Brini
Intracellular membrane contact sites (MCSs) between organelles have crucial roles in cellular signalling and homeostasis. These sites, which are often disrupted in pathological conditions, enable the exchange of ions, lipids and metabolites between membrane-bound compartments, helping cells adapt to varying physiological conditions. Specific tether proteins and complexes stabilize these interactions and mediate responses to different intracellular or extracellular stimuli. The study of MCSs has progressed in recent years, owing to the development of new methods such as genetically encoded reporter constructs, advanced imaging techniques, including super-resolution microscopy and electron tomography, and proteomic approaches based on mass spectrometry. These tools have enabled unprecedented visualization and quantification of organelle interactions, as well as identification of the molecular players involved. This Expert Recommendation aims to define and map the ‘organelle contactome’, describing key proteins involved in contact site formation and the roles of MCSs in cellular function. We also explore contact site dynamics and detail advantages and disadvantages of the methodologies for studying them. Importantly, we consolidate open questions in contact site research and discuss challenges and limitations of the current experimental approaches. Membrane contact sites between organelles facilitate the exchange of ions, lipids and metabolites. This Expert Recommendation highlights recent advances in defining the organelle contactome and discusses challenges and future directions in membrane contact site research.
{"title":"Key challenges and recommendations for defining organelle membrane contact sites","authors":"Tito Calì, Emmanuelle M. Bayer, Emily R. Eden, György Hajnóczky, Benoit Kornmann, Laura Lackner, Jen Liou, Karin Reinisch, Hyun-Woo Rhee, Rosario Rizzuto, Luca Scorrano, Marisa Brini","doi":"10.1038/s41580-025-00864-x","DOIUrl":"10.1038/s41580-025-00864-x","url":null,"abstract":"Intracellular membrane contact sites (MCSs) between organelles have crucial roles in cellular signalling and homeostasis. These sites, which are often disrupted in pathological conditions, enable the exchange of ions, lipids and metabolites between membrane-bound compartments, helping cells adapt to varying physiological conditions. Specific tether proteins and complexes stabilize these interactions and mediate responses to different intracellular or extracellular stimuli. The study of MCSs has progressed in recent years, owing to the development of new methods such as genetically encoded reporter constructs, advanced imaging techniques, including super-resolution microscopy and electron tomography, and proteomic approaches based on mass spectrometry. These tools have enabled unprecedented visualization and quantification of organelle interactions, as well as identification of the molecular players involved. This Expert Recommendation aims to define and map the ‘organelle contactome’, describing key proteins involved in contact site formation and the roles of MCSs in cellular function. We also explore contact site dynamics and detail advantages and disadvantages of the methodologies for studying them. Importantly, we consolidate open questions in contact site research and discuss challenges and limitations of the current experimental approaches. Membrane contact sites between organelles facilitate the exchange of ions, lipids and metabolites. This Expert Recommendation highlights recent advances in defining the organelle contactome and discusses challenges and future directions in membrane contact site research.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 10","pages":"776-796"},"PeriodicalIF":90.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41580-025-00864-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1038/s41580-025-00857-w
Vincent Jung, Cédric Vincent-Cuaz, Charlotte Tumescheit, Lisa Fournier, Marousa Darsinou, Zhi Ming Xu, Ali Saadat, Yiran Wang, Petros Tsantoulis, Olivier Michielin, Jacques Fellay, Rickie Patani, Andres Ramos, Pascal Frossard, Janna Hastings, Antonella Riccio, Lonneke van der Plas, Raphaëlle Luisier
In addition to encoding proteins, mRNAs have context-specific regulatory roles that contribute to many cellular processes. However, uncovering new mRNA functions is constrained by limitations of traditional biochemical and computational methods. In this Roadmap, we highlight how artificial intelligence can transform our understanding of RNA biology by fostering collaborations between RNA biologists and computational scientists to drive innovation in this fundamental field of research. We discuss how non-coding regions of the mRNA, including introns and 5′ and 3′ untranslated regions, regulate the metabolism and interactomes of mRNA, and the current challenges in characterizing these regions. We further discuss large language models, which can be used to learn biologically meaningful RNA sequence representations. We also provide a detailed roadmap for integrating large language models with graph neural networks to harness publicly available sequencing and knowledge data. Adopting this roadmap will allow us to predict RNA interactions with diverse molecules and the modelling of context-specific mRNA interactomes. Studying RNA function is constrained by limitations of traditional methods. This Roadmap discusses how artificial intelligence (AI) can enhance the study of how non-coding regions of mRNA regulate its function, and suggests how to use AI to harness publicly available data towards that goal.
{"title":"Decoding the interactions and functions of non-coding RNA with artificial intelligence","authors":"Vincent Jung, Cédric Vincent-Cuaz, Charlotte Tumescheit, Lisa Fournier, Marousa Darsinou, Zhi Ming Xu, Ali Saadat, Yiran Wang, Petros Tsantoulis, Olivier Michielin, Jacques Fellay, Rickie Patani, Andres Ramos, Pascal Frossard, Janna Hastings, Antonella Riccio, Lonneke van der Plas, Raphaëlle Luisier","doi":"10.1038/s41580-025-00857-w","DOIUrl":"10.1038/s41580-025-00857-w","url":null,"abstract":"In addition to encoding proteins, mRNAs have context-specific regulatory roles that contribute to many cellular processes. However, uncovering new mRNA functions is constrained by limitations of traditional biochemical and computational methods. In this Roadmap, we highlight how artificial intelligence can transform our understanding of RNA biology by fostering collaborations between RNA biologists and computational scientists to drive innovation in this fundamental field of research. We discuss how non-coding regions of the mRNA, including introns and 5′ and 3′ untranslated regions, regulate the metabolism and interactomes of mRNA, and the current challenges in characterizing these regions. We further discuss large language models, which can be used to learn biologically meaningful RNA sequence representations. We also provide a detailed roadmap for integrating large language models with graph neural networks to harness publicly available sequencing and knowledge data. Adopting this roadmap will allow us to predict RNA interactions with diverse molecules and the modelling of context-specific mRNA interactomes. Studying RNA function is constrained by limitations of traditional methods. This Roadmap discusses how artificial intelligence (AI) can enhance the study of how non-coding regions of mRNA regulate its function, and suggests how to use AI to harness publicly available data towards that goal.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 10","pages":"797-818"},"PeriodicalIF":90.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319501","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 : 2025-06-10DOI: 10.1038/s41580-025-00868-7
Roser Vento-Tormo
A machine learning model was trained to quantify how closely neurons differentiated in a dish from stem cells resemble those found in the brain.
一个机器学习模型被训练用来量化培养皿中从干细胞中分化出来的神经元与大脑中发现的神经元的接近程度。
{"title":"How machine learning can help us understand what we have grown in the dish","authors":"Roser Vento-Tormo","doi":"10.1038/s41580-025-00868-7","DOIUrl":"10.1038/s41580-025-00868-7","url":null,"abstract":"A machine learning model was trained to quantify how closely neurons differentiated in a dish from stem cells resemble those found in the brain.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"585-585"},"PeriodicalIF":81.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252302","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 : 2025-06-05DOI: 10.1038/s41580-025-00858-9
Kevin J. Cheung, Sally Horne-Badovinac
Migrating cells have key functions in shaping tissues during development, repairing tissues after development and supporting cancer invasion and metastasis. In all these contexts, cells often maintain contact with their neighbours and move as a group, in a process termed collective migration. In this Review, we describe the elegant mechanisms used by collectively migrating cells in vivo to coordinate their movements and obtain directional information. We start by highlighting the diverse physiological roles that migrating collectives have within the body and then focus on dominant paradigms for the organization of migrating collectives including the roles of leader and follower cells, local cell–cell adhesion and signalling, and external guidance cues. By comparing collective migrations occurring during development and cancer, we bring into focus shared principles for collective cell movement and distinct strategies used by cancer cells for their own dispersal. Throughout, we pay particular attention to how migrating collectives display emergent properties not exhibited by individually migrating cells and how these properties provide the robustness needed for efficient cell movement. Collective cell migration has major roles in animal development, tissue repair and cancer metastasis. This Review explores how migrating collectives are organized in development versus cancer, focusing on cell adhesion, signalling and guidance cues.
{"title":"Collective migration modes in development, tissue repair and cancer","authors":"Kevin J. Cheung, Sally Horne-Badovinac","doi":"10.1038/s41580-025-00858-9","DOIUrl":"10.1038/s41580-025-00858-9","url":null,"abstract":"Migrating cells have key functions in shaping tissues during development, repairing tissues after development and supporting cancer invasion and metastasis. In all these contexts, cells often maintain contact with their neighbours and move as a group, in a process termed collective migration. In this Review, we describe the elegant mechanisms used by collectively migrating cells in vivo to coordinate their movements and obtain directional information. We start by highlighting the diverse physiological roles that migrating collectives have within the body and then focus on dominant paradigms for the organization of migrating collectives including the roles of leader and follower cells, local cell–cell adhesion and signalling, and external guidance cues. By comparing collective migrations occurring during development and cancer, we bring into focus shared principles for collective cell movement and distinct strategies used by cancer cells for their own dispersal. Throughout, we pay particular attention to how migrating collectives display emergent properties not exhibited by individually migrating cells and how these properties provide the robustness needed for efficient cell movement. Collective cell migration has major roles in animal development, tissue repair and cancer metastasis. This Review explores how migrating collectives are organized in development versus cancer, focusing on cell adhesion, signalling and guidance cues.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 10","pages":"741-758"},"PeriodicalIF":90.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228678","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 : 2025-06-04DOI: 10.1038/s41580-025-00866-9
Eytan Zlotorynski
Nucleosomes — the basic unit of chromatin architecture — have intrinsic biophysical features of large-scale genome organization.
核小体是染色质结构的基本单位，具有大规模基因组组织的内在生物物理特征。
{"title":"Nucleosomes as blueprints of genome architecture","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-025-00866-9","DOIUrl":"10.1038/s41580-025-00866-9","url":null,"abstract":"Nucleosomes — the basic unit of chromatin architecture — have intrinsic biophysical features of large-scale genome organization.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 7","pages":"500-500"},"PeriodicalIF":81.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211403","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 : 2025-05-21DOI: 10.1038/s41580-025-00862-z
Kyrillos S. Abdallah
In this Tools of the Trade article, Abdallah (Gilbert lab) describes the development of direct analysis of ribosome targeting (DART), a tool designed to explore 5' UTR sequences for their potential to efficiently initiate translation.
{"title":"Uncovering mRNA sequences that control translation initiation","authors":"Kyrillos S. Abdallah","doi":"10.1038/s41580-025-00862-z","DOIUrl":"10.1038/s41580-025-00862-z","url":null,"abstract":"In this Tools of the Trade article, Abdallah (Gilbert lab) describes the development of direct analysis of ribosome targeting (DART), a tool designed to explore 5' UTR sequences for their potential to efficiently initiate translation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 9","pages":"645-645"},"PeriodicalIF":90.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104113","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 : 2025-05-21DOI: 10.1038/s41580-025-00847-y
Matthew P. Johnson
The electron transfer chain of chloroplast thylakoid membranes uses solar energy to split water into electrons and protons, creating energetic gradients that drive the formation of photosynthetic fuel in the form of NADPH and ATP. These metabolites are then used to power the fixation of carbon dioxide into biomass through the Calvin–Benson–Bassham cycle in the chloroplast stroma. Recent advances in molecular genetics, structural biology and spectroscopy have provided an unprecedented understanding of the molecular events involved in photosynthetic electron transfer from photon capture to ATP production. Specifically, we have gained insights into the assembly of the photosynthetic complexes into larger supercomplexes, thylakoid membrane organization and the mechanisms underpinning efficient light harvesting, photoprotection and oxygen evolution. In this Review, I focus on the angiosperm plant thylakoid system, outlining our current knowledge on the structure, function, regulation and assembly of each component of the photosynthetic chain. I explain how solar energy is harvested and converted into chemical energy by the photosynthetic electron transfer chain, how its components are integrated into a complex membrane macrostructure and how this organization contributes to regulation and photoprotection. The electron transfer chain in chloroplast thylakoid membranes uses solar energy to produce NADPH and ATP, which power carbon fixation into biomass. This Review discusses the structure and function of the core photosynthesis complexes and provides recent insights into their regulation and assembly.
{"title":"Structure, regulation and assembly of the photosynthetic electron transport chain","authors":"Matthew P. Johnson","doi":"10.1038/s41580-025-00847-y","DOIUrl":"10.1038/s41580-025-00847-y","url":null,"abstract":"The electron transfer chain of chloroplast thylakoid membranes uses solar energy to split water into electrons and protons, creating energetic gradients that drive the formation of photosynthetic fuel in the form of NADPH and ATP. These metabolites are then used to power the fixation of carbon dioxide into biomass through the Calvin–Benson–Bassham cycle in the chloroplast stroma. Recent advances in molecular genetics, structural biology and spectroscopy have provided an unprecedented understanding of the molecular events involved in photosynthetic electron transfer from photon capture to ATP production. Specifically, we have gained insights into the assembly of the photosynthetic complexes into larger supercomplexes, thylakoid membrane organization and the mechanisms underpinning efficient light harvesting, photoprotection and oxygen evolution. In this Review, I focus on the angiosperm plant thylakoid system, outlining our current knowledge on the structure, function, regulation and assembly of each component of the photosynthetic chain. I explain how solar energy is harvested and converted into chemical energy by the photosynthetic electron transfer chain, how its components are integrated into a complex membrane macrostructure and how this organization contributes to regulation and photoprotection. The electron transfer chain in chloroplast thylakoid membranes uses solar energy to produce NADPH and ATP, which power carbon fixation into biomass. This Review discusses the structure and function of the core photosynthesis complexes and provides recent insights into their regulation and assembly.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 9","pages":"667-690"},"PeriodicalIF":90.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113689","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 : 2025-05-21DOI: 10.1038/s41580-025-00863-y
Xiaowei Zhang, Luis S. Mille-Fragoso
In this Tools of the Trade article, Zhang and Mille-Fragoso (Gao lab) describe a synthetic receptor platform that is activated by the binding of specific ligands, which triggers RNA editing, enabling the translation of an output protein.
{"title":"Enabling RNA-compatible synthetic receptors through RNA editing","authors":"Xiaowei Zhang, Luis S. Mille-Fragoso","doi":"10.1038/s41580-025-00863-y","DOIUrl":"10.1038/s41580-025-00863-y","url":null,"abstract":"In this Tools of the Trade article, Zhang and Mille-Fragoso (Gao lab) describe a synthetic receptor platform that is activated by the binding of specific ligands, which triggers RNA editing, enabling the translation of an output protein.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"581-581"},"PeriodicalIF":81.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104100","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 : 2025-05-20DOI: 10.1038/s41580-025-00852-1
Nan Luo, Qiang Huang, Meiling Zhang, Chengqi Yi
The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the ‘fifth nucleotide’ of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application. Pseudouridine is a long-discovered RNA modification that has lately attracted much renewed interest. This Review discusses the emerging functions of pseudouridine in gene regulation and mitochondrial function, and its therapeutic potential following the successful use of pseudouridylation in SARS-CoV-2 mRNA vaccines.
{"title":"Functions and therapeutic applications of pseudouridylation","authors":"Nan Luo, Qiang Huang, Meiling Zhang, Chengqi Yi","doi":"10.1038/s41580-025-00852-1","DOIUrl":"10.1038/s41580-025-00852-1","url":null,"abstract":"The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the ‘fifth nucleotide’ of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application. Pseudouridine is a long-discovered RNA modification that has lately attracted much renewed interest. This Review discusses the emerging functions of pseudouridine in gene regulation and mitochondrial function, and its therapeutic potential following the successful use of pseudouridylation in SARS-CoV-2 mRNA vaccines.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 9","pages":"691-705"},"PeriodicalIF":90.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097188","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 : 2025-05-19DOI: 10.1038/s41580-025-00855-y
Kevin P. Guay, Wen-Chuan Chou, Nathan P. Canniff, Kylie B. Paul, Daniel N. Hebert
The vast majority of proteins that traverse the mammalian secretory pathway become N-glycosylated in the endoplasmic reticulum (ER). The bulky glycan protein modifications, which are conserved in fungi and humans, act as maturation and quality-control tags. In this Review, we discuss findings published in the past decade that have rapidly expanded our understanding of the transfer and processing of N-glycans, as well as their role in protein maturation, quality control and trafficking in the ER, facilitated by structural insights into the addition of N-glycans by the oligosaccharyltransferases A and B (OST-A and OST-B). These findings suggest that N-glycans serve as reporters of the folding status of secretory proteins as they traverse the ER, enabling the lectin chaperones to guide their maturation. We also explore how the emergence of co-translational glycosylation and the expansion of the glycoproteostasis network in metazoans has expanded the role of N-glycans in early protein-maturation events and quality control. N-glycosylation of secretory pathway proteins in the ER is crucial for their maturation and quality control. Recent insights into the enzymes and chaperones that facilitate N-glycosylation have expanded our understanding of the glycoproteostasis network in metazoans.
{"title":"N-glycan-dependent protein maturation and quality control in the ER","authors":"Kevin P. Guay, Wen-Chuan Chou, Nathan P. Canniff, Kylie B. Paul, Daniel N. Hebert","doi":"10.1038/s41580-025-00855-y","DOIUrl":"10.1038/s41580-025-00855-y","url":null,"abstract":"The vast majority of proteins that traverse the mammalian secretory pathway become N-glycosylated in the endoplasmic reticulum (ER). The bulky glycan protein modifications, which are conserved in fungi and humans, act as maturation and quality-control tags. In this Review, we discuss findings published in the past decade that have rapidly expanded our understanding of the transfer and processing of N-glycans, as well as their role in protein maturation, quality control and trafficking in the ER, facilitated by structural insights into the addition of N-glycans by the oligosaccharyltransferases A and B (OST-A and OST-B). These findings suggest that N-glycans serve as reporters of the folding status of secretory proteins as they traverse the ER, enabling the lectin chaperones to guide their maturation. We also explore how the emergence of co-translational glycosylation and the expansion of the glycoproteostasis network in metazoans has expanded the role of N-glycans in early protein-maturation events and quality control. N-glycosylation of secretory pathway proteins in the ER is crucial for their maturation and quality control. Recent insights into the enzymes and chaperones that facilitate N-glycosylation have expanded our understanding of the glycoproteostasis network in metazoans.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 12","pages":"926-939"},"PeriodicalIF":90.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097136","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：