Pub Date : 2026-03-19DOI: 10.1038/s41580-026-00957-1
William Leineweber,Reika Tei,Anna Mäkiniemi,Alice Ting,Emma Lundberg
How proteins localize to specific compartments, function in coordination with other biomolecules and, ultimately, contribute to diverse cellular activities are crucial questions in cell biology. Complicating the answers to these questions are multilocalizing and multifunctional proteins, whose impact on the cell depends on both spatial and temporal contexts. Therefore, contextualizing protein functions based on their subcellular localization is necessary to fully understand cell behaviours. Recent advances in instrumentation and protein labelling techniques are rapidly increasing the availability of tools, technologies and applications that measure and control protein localization and compartment-specific function. In this Review, we first discuss microscopy, mass spectrometry-based correlation profiling and proximity labelling methods that assign localizations to proteins, ranging from cellular compartments to protein-protein interactions. We next examine the available tools for manipulating protein localization and measuring the effects of these manipulations, including localization tags and bifunctional molecules. For each technology, we assess the strengths and weaknesses that ultimately determine their usefulness. We conclude with an outlook on future technological advances in the field of spatial subcellular proteomics and their potential implications for cell biology and clinical applications.
{"title":"Technologies to measure and modulate protein subcellular localization.","authors":"William Leineweber,Reika Tei,Anna Mäkiniemi,Alice Ting,Emma Lundberg","doi":"10.1038/s41580-026-00957-1","DOIUrl":"https://doi.org/10.1038/s41580-026-00957-1","url":null,"abstract":"How proteins localize to specific compartments, function in coordination with other biomolecules and, ultimately, contribute to diverse cellular activities are crucial questions in cell biology. Complicating the answers to these questions are multilocalizing and multifunctional proteins, whose impact on the cell depends on both spatial and temporal contexts. Therefore, contextualizing protein functions based on their subcellular localization is necessary to fully understand cell behaviours. Recent advances in instrumentation and protein labelling techniques are rapidly increasing the availability of tools, technologies and applications that measure and control protein localization and compartment-specific function. In this Review, we first discuss microscopy, mass spectrometry-based correlation profiling and proximity labelling methods that assign localizations to proteins, ranging from cellular compartments to protein-protein interactions. We next examine the available tools for manipulating protein localization and measuring the effects of these manipulations, including localization tags and bifunctional molecules. For each technology, we assess the strengths and weaknesses that ultimately determine their usefulness. We conclude with an outlook on future technological advances in the field of spatial subcellular proteomics and their potential implications for cell biology and clinical applications.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"11 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483618","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 : 2026-03-06DOI: 10.1038/s41580-026-00960-6
Lisa Heinke
{"title":"Overcoming cytoskeleton instability in the early embryo.","authors":"Lisa Heinke","doi":"10.1038/s41580-026-00960-6","DOIUrl":"https://doi.org/10.1038/s41580-026-00960-6","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368440","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 : 2026-03-04DOI: 10.1038/s41580-026-00949-1
Jan Stundl,Ayyappa Raja Desingu Rajan,Marianne E Bronner
The neural crest is an important stem cell population characterized by its multipotency, migratory behaviour and broad ability to differentiate into numerous derivatives throughout the vertebrate body, as diverse as cell types contributing to the cardiovascular system, craniofacial skeleton, peripheral nervous system and pigmentation of the skin. The developmental trajectory of the neural crest is governed by a complex gene regulatory network (GRN) that mediates induction and specification at the neural plate border, emergence of neural crest cells (NCCs) from the neural tube, their migration through the periphery and cell fate determination en route to different final destinations. In this Review, we discuss the significant progress in investigating the neural crest GRN, which has increased our understanding of how NCCs impact vertebrate development and evolution, their role in adult tissue regeneration and their contribution to diseases derived from abnormalities in NCCs.
{"title":"Neural crest gene regulatory networks as drivers of development, diversification and disease.","authors":"Jan Stundl,Ayyappa Raja Desingu Rajan,Marianne E Bronner","doi":"10.1038/s41580-026-00949-1","DOIUrl":"https://doi.org/10.1038/s41580-026-00949-1","url":null,"abstract":"The neural crest is an important stem cell population characterized by its multipotency, migratory behaviour and broad ability to differentiate into numerous derivatives throughout the vertebrate body, as diverse as cell types contributing to the cardiovascular system, craniofacial skeleton, peripheral nervous system and pigmentation of the skin. The developmental trajectory of the neural crest is governed by a complex gene regulatory network (GRN) that mediates induction and specification at the neural plate border, emergence of neural crest cells (NCCs) from the neural tube, their migration through the periphery and cell fate determination en route to different final destinations. In this Review, we discuss the significant progress in investigating the neural crest GRN, which has increased our understanding of how NCCs impact vertebrate development and evolution, their role in adult tissue regeneration and their contribution to diseases derived from abnormalities in NCCs.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"227 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350699","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 : 2026-02-19DOI: 10.1038/s41580-026-00955-3
Alison C. Mody
{"title":"Probing the effects of protein glycosylation on transcription with induced-proximity tools","authors":"Alison C. Mody","doi":"10.1038/s41580-026-00955-3","DOIUrl":"https://doi.org/10.1038/s41580-026-00955-3","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"7 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223276","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 : 2026-02-18DOI: 10.1038/s41580-026-00947-3
Alina Sigaeva, Charlotte Hutchings, Anthony Cesnik, Kathryn S Lilley, Emma Lundberg
Biological functions depend on the spatiotemporal distribution of proteins within cells. Key cellular activities such as signal transduction, metabolism, cell cycle and cell death are driven by the interactions of proteins that are localized in multiple cellular compartments. Such multilocalization can even allow protein with identical sequences to display multifunctionality, a phenomenon known as moonlighting. Despite its biological importance, the relationship between protein localization and function remains underexplored. In this Review, we discuss the known mechanisms of protein localization (including RNA transport, role of proteoforms and molecular interactions) and how subcellular localization controls protein function. Proper regulation of protein localization is crucial for specialized cell and tissue functions, including cell differentiation, polarization and the epithelial-mesenchymal transition. Protein mislocalization can also have important roles in pathological processes, such as in cancer, neurodegeneration and autoimmunity. We end with a discussion of current technological and conceptual challenges in the field of subcellular proteomics and spatial biology. Addressing these challenges will allow us to link the dynamic nature of protein localization and function across biological scales and contexts, with great impact on fundamental cell biology and clinical applications.
{"title":"Subcellular localization as a driver of protein function.","authors":"Alina Sigaeva, Charlotte Hutchings, Anthony Cesnik, Kathryn S Lilley, Emma Lundberg","doi":"10.1038/s41580-026-00947-3","DOIUrl":"https://doi.org/10.1038/s41580-026-00947-3","url":null,"abstract":"<p><p>Biological functions depend on the spatiotemporal distribution of proteins within cells. Key cellular activities such as signal transduction, metabolism, cell cycle and cell death are driven by the interactions of proteins that are localized in multiple cellular compartments. Such multilocalization can even allow protein with identical sequences to display multifunctionality, a phenomenon known as moonlighting. Despite its biological importance, the relationship between protein localization and function remains underexplored. In this Review, we discuss the known mechanisms of protein localization (including RNA transport, role of proteoforms and molecular interactions) and how subcellular localization controls protein function. Proper regulation of protein localization is crucial for specialized cell and tissue functions, including cell differentiation, polarization and the epithelial-mesenchymal transition. Protein mislocalization can also have important roles in pathological processes, such as in cancer, neurodegeneration and autoimmunity. We end with a discussion of current technological and conceptual challenges in the field of subcellular proteomics and spatial biology. Addressing these challenges will allow us to link the dynamic nature of protein localization and function across biological scales and contexts, with great impact on fundamental cell biology and clinical applications.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":90.2,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220354","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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