Mainak Bose, Branislava Rankovic, Julia Mahamid, Anne Ephrussi
{"title":"An architectural role of specific RNA–RNA interactions in oskar granules","authors":"Mainak Bose, Branislava Rankovic, Julia Mahamid, Anne Ephrussi","doi":"10.1038/s41556-024-01519-3","DOIUrl":"10.1038/s41556-024-01519-3","url":null,"abstract":"Ribonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins. Studies have shown that RNA tunes the phase behaviour of RNA-binding proteins, but the role of intermolecular RNA–RNA interactions in RNP granules in vivo remains less explored. Here we determine the role of a sequence-specific RNA–RNA kissing-loop interaction in assembly of mesoscale oskar RNP granules in the female Drosophila germline. We show that a two-nucleotide mutation that disrupts kissing-loop-mediated oskar messenger RNA dimerization impairs condensate formation in vitro and oskar granule assembly in the developing oocyte, leading to defective posterior localization of the RNA and abrogation of oskar-associated processing bodies upon nutritional stress. This specific trans RNA–RNA interaction acts synergistically with the scaffold RNA-binding protein, Bruno, in driving condensate assembly. Our study highlights the architectural contribution of an mRNA and its specific secondary structure and tertiary interactions to the formation of an RNP granule that is essential for embryonic development. Bose, Rankovic et al. show that a specific RNA–RNA kissing-loop interaction plays a crucial role in driving biomolecular condensation of ribonucleoprotein granules in the Drosophila germline.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1934-1942"},"PeriodicalIF":17.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01519-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330377","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}
{"title":"Astrocytes are enablers of brain metastases","authors":"Livia Garzia","doi":"10.1038/s41556-024-01516-6","DOIUrl":"10.1038/s41556-024-01516-6","url":null,"abstract":"Circulating tumour cells from primary carcinomas may reach the brain and establish metastases. In the brain parenchyma, tumour cells initiate extensive interactions with resident astrocytes, microglia and neurons, forming a niche where tumour cells can thrive. A new study reveals a previously unknown type of astrocyte–tumour cell interaction.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1632-1633"},"PeriodicalIF":17.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329656","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}
Shan Wang, Emelie Englund, Pontus Kjellman, Zhen Li, Johannes Kumra Ahnlide, Carmen Rodriguez-Cupello, Mattia Saggioro, Ryu Kanzaki, Kristian Pietras, David Lindgren, Håkan Axelson, Christelle N. Prinz, Vinay Swaminathan, Chris D. Madsen
{"title":"Retraction Note: CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling","authors":"Shan Wang, Emelie Englund, Pontus Kjellman, Zhen Li, Johannes Kumra Ahnlide, Carmen Rodriguez-Cupello, Mattia Saggioro, Ryu Kanzaki, Kristian Pietras, David Lindgren, Håkan Axelson, Christelle N. Prinz, Vinay Swaminathan, Chris D. Madsen","doi":"10.1038/s41556-024-01531-7","DOIUrl":"10.1038/s41556-024-01531-7","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1817-1817"},"PeriodicalIF":17.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01531-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308162","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}
{"title":"Inverse bleb membrane protrusions pump fluid within the early mouse embryo","authors":"","doi":"10.1038/s41556-024-01510-y","DOIUrl":"10.1038/s41556-024-01510-y","url":null,"abstract":"During early mouse development, a fluid-filled lumen inflates the embryo. Membrane protrusions called inverse blebs have been found to form at cell–cell contacts. Cycles of inverse bleb filling and unloading act as hydraulic pumps and contribute to the formation of the lumen.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1637-1638"},"PeriodicalIF":17.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275149","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}
Arseniy E. Yuzhalin, Frank J. Lowery, Yohei Saito, Xiangliang Yuan, Jun Yao, Yimin Duan, Jingzhen Ding, Sunil Acharya, Chenyu Zhang, Abigail Fajardo, Hao-Nien Chen, Yongkun Wei, Yutong Sun, Lin Zhang, Yi Xiao, Ping Li, Philip L. Lorenzi, Jason T. Huse, Huihui Fan, Zhongming Zhao, Mien-Chie Hung, Dihua Yu
{"title":"Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition","authors":"Arseniy E. Yuzhalin, Frank J. Lowery, Yohei Saito, Xiangliang Yuan, Jun Yao, Yimin Duan, Jingzhen Ding, Sunil Acharya, Chenyu Zhang, Abigail Fajardo, Hao-Nien Chen, Yongkun Wei, Yutong Sun, Lin Zhang, Yi Xiao, Ping Li, Philip L. Lorenzi, Jason T. Huse, Huihui Fan, Zhongming Zhao, Mien-Chie Hung, Dihua Yu","doi":"10.1038/s41556-024-01509-5","DOIUrl":"10.1038/s41556-024-01509-5","url":null,"abstract":"Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1–Stat1–importin α–Nlrc5 pathway, enabling BrMs to avoid recognition by T cells. Treatment with roscovitine—a clinically applicable Cdk5 inhibitor—alone or combined with immune checkpoint inhibitors, significantly reduces BrM burden and increases tumour-infiltrating functional CD8+ lymphocytes in mice. Thus, astrocyte-induced Cdk5 overexpression endorses BrM immune evasion, whereas therapeutically targeting Cdk5 markedly improves the efficacy of immune checkpoint inhibitors and inhibits BrM growth. Yuzhalin et al. report that astrocyte-mediated upregulation of Cdk5 in metastatic breast cancer cells inhibits MHC-I expression on the cell surface, thereby enabling escape from killing by CD8+ T cells and facilitating brain metastasis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1773-1789"},"PeriodicalIF":17.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275150","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}
Nada Al-Refaie, Francesco Padovani, Johanna Hornung, Lorenz Pudelko, Francesca Binando, Andrea del Carmen Fabregat, Qiuxia Zhao, Benjamin D. Towbin, Elif Sarinay Cenik, Nicholas Stroustrup, Jan Padeken, Kurt M. Schmoller, Daphne S. Cabianca
{"title":"Fasting shapes chromatin architecture through an mTOR/RNA Pol I axis","authors":"Nada Al-Refaie, Francesco Padovani, Johanna Hornung, Lorenz Pudelko, Francesca Binando, Andrea del Carmen Fabregat, Qiuxia Zhao, Benjamin D. Towbin, Elif Sarinay Cenik, Nicholas Stroustrup, Jan Padeken, Kurt M. Schmoller, Daphne S. Cabianca","doi":"10.1038/s41556-024-01512-w","DOIUrl":"10.1038/s41556-024-01512-w","url":null,"abstract":"Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom, yet how it impacts three-dimensional (3D) genome organization is unknown. Here we show that fasting induces an intestine-specific, reversible and large-scale spatial reorganization of chromatin in Caenorhabditis elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, acting through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodelling of the nucleolus. By uncoupling the 3D genome configuration from the animal’s nutritional status, we find that the expression of metabolic and stress-related genes increases when the spatial reorganization of chromatin occurs, showing that the 3D genome might support the transcriptional response in fasted animals. Our work documents a large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients. Al-Refaie et al. show that fasting induces spatial reorganization of chromatin and formation of chromatin rings in an mTORC1- and RNA Pol I-dependent manner in the C. elegans intestine.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1903-1917"},"PeriodicalIF":17.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01512-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245272","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}
Jiachao Xu, Yu Liang, Nan Li, Song Dang, Amin Jiang, Yiqun Liu, Yuting Guo, Xiaoyu Yang, Yi Yuan, Xinyi Zhang, Yaran Yang, Yongtao Du, Anbing Shi, Xiaoyun Liu, Dong Li, Kangmin He
{"title":"Clathrin-associated carriers enable recycling through a kiss-and-run mechanism","authors":"Jiachao Xu, Yu Liang, Nan Li, Song Dang, Amin Jiang, Yiqun Liu, Yuting Guo, Xiaoyu Yang, Yi Yuan, Xinyi Zhang, Yaran Yang, Yongtao Du, Anbing Shi, Xiaoyun Liu, Dong Li, Kangmin He","doi":"10.1038/s41556-024-01499-4","DOIUrl":"10.1038/s41556-024-01499-4","url":null,"abstract":"Endocytosis and recycling control the uptake and retrieval of various materials, including membrane proteins and lipids, in all eukaryotic cells. These processes are crucial for cell growth, organization, function and environmental communication. However, the mechanisms underlying efficient, fast endocytic recycling remain poorly understood. Here, by utilizing a biosensor and imaging-based screening, we uncover a recycling mechanism that couples endocytosis and fast recycling, which we name the clathrin-associated fast endosomal recycling pathway (CARP). Clathrin-associated tubulovesicular carriers containing clathrin, AP1, Arf1, Rab1 and Rab11, while lacking the multimeric retrieval complexes, are generated at subdomains of early endosomes and then transported along actin to cell surfaces. Unexpectedly, the clathrin-associated recycling carriers undergo partial fusion with the plasma membrane. Subsequently, they are released from the membrane by dynamin and re-enter cells. Multiple receptors utilize and modulate CARP for fast recycling following endocytosis. Thus, CARP represents a previously unrecognized endocytic recycling mechanism with kiss-and-run membrane fusion. Xu, Liang, Li, Dang et al. delineate the clathrin-associated fast endosomal recycling pathway, which involves clathrin-associated carriers derived from early endosomes partially fusing with the plasma membrane before release from the membrane.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1652-1668"},"PeriodicalIF":17.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245273","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}
Yang Yang, Luis A. Valencia, Chih-Hao Lu, Melissa L. Nakamoto, Ching-Ting Tsai, Chun Liu, Huaxiao Yang, Wei Zhang, Zeinab Jahed, Wan-Ru Lee, Francesca Santoro, Jen Liou, Joseph C. Wu, Bianxiao Cui
{"title":"Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum","authors":"Yang Yang, Luis A. Valencia, Chih-Hao Lu, Melissa L. Nakamoto, Ching-Ting Tsai, Chun Liu, Huaxiao Yang, Wei Zhang, Zeinab Jahed, Wan-Ru Lee, Francesca Santoro, Jen Liou, Joseph C. Wu, Bianxiao Cui","doi":"10.1038/s41556-024-01511-x","DOIUrl":"10.1038/s41556-024-01511-x","url":null,"abstract":"Contact sites between the endoplasmic reticulum (ER) and plasma membrane (PM) play a crucial role in governing calcium regulation and lipid homeostasis. Despite their significance, the factors regulating their spatial distribution on the PM remain elusive. Inspired by observations in cardiomyocytes, where ER–PM contact sites concentrate on tubular PM invaginations known as transverse tubules, we hypothesize that PM curvature plays a role in ER–PM contact formation. Through precise control of PM invaginations, we show that PM curvatures locally induce the formation of ER–PM contacts in cardiomyocytes. Intriguingly, the junctophilin family of ER–PM tethering proteins, specifically expressed in excitable cells, is the key player in this process, whereas the ubiquitously expressed extended synaptotagmin-2 does not show a preference for PM curvature. At the mechanistic level, we find that the low-complexity region (LCR) and membrane occupation and recognition nexus (MORN) motifs of junctophilins can bind independently to the PM, but both the LCR and MORN motifs are required for targeting PM curvatures. By examining the junctophilin interactome, we identify a family of curvature-sensing proteins—Eps15 homology domain-containing proteins—that interact with the MORN_LCR motifs and facilitate the preferential tethering of junctophilins to curved PM. These findings highlight the pivotal role of PM curvature in the formation of ER–PM contacts in cardiomyocytes and unveil a mechanism for the spatial regulation of ER–PM contacts through PM curvature modulation. Yang et al. show that plasma membrane curvature promotes the site-specific formation of contacts with the endoplasmic reticulum through junctophilin-2 tethers in cardiomyocytes.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1878-1891"},"PeriodicalIF":17.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01511-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235150","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}
{"title":"Navigating the biology of cell death","authors":"","doi":"10.1038/s41556-024-01515-7","DOIUrl":"10.1038/s41556-024-01515-7","url":null,"abstract":"This issue presents a Focus of specially commissioned articles that discuss cell death in its multiple forms, implications for homeostatic physiology and disease and outstanding questions in this expanding field.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 9","pages":"1373-1373"},"PeriodicalIF":17.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01515-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174386","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}