Nature Cell Biology最新文献

Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum 质膜曲率调节与内质网接触的形成

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-17 DOI: 10.1038/s41556-024-01511-x

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":"https://doi.org/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.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ribotoxic stress drives cell death by UV 核糖酸应激促使细胞死于紫外线

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01506-8

Petra Gross

引用次数: 0

Navigating the biology of cell death 细胞死亡生物学导航

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01515-7

引用次数: 0

Mitophagy protects against ferroptosis 有丝分裂可防止铁蛋白沉积症

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01507-7

Petra Gross

引用次数: 0

Solid tumour-induced systemic immunosuppression involves dichotomous myeloid–B cell interactions 实体瘤诱导的全身免疫抑制涉及二分法髓系-B 细胞相互作用

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01508-6

Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno, Bora Lim, Xiang H.-F. Zhang

{"title":"Solid tumour-induced systemic immunosuppression involves dichotomous myeloid–B cell interactions","authors":"Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno, Bora Lim, Xiang H.-F. Zhang","doi":"10.1038/s41556-024-01508-6","DOIUrl":"https://doi.org/10.1038/s41556-024-01508-6","url":null,"abstract":"Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from the peripheral blood of patients with triple-negative breast cancer recapitulate the TiBA subtypes, and the distinct TiBA profile correlates with pathologic complete responses to standard-of-care immunotherapy. This study underscores the inter-patient diversity of tumour-induced systemic changes and emphasizes the need for treatments tailored to different B and myeloid cell abnormalities.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170869","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

Ferroptosis disseminates afar in development 铁蛋白沉积症在发育过程中四处扩散

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01504-w

Zhe Wang

引用次数: 0

Profiling cell death in COVID-19 pathology 剖析 COVID-19 病理学中的细胞死亡

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01505-9

Zhe Wang

引用次数: 0

The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription 多角体系统通过限制启动前复合物的形成来抵消转录，从而使启动子处于深度关闭状态

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01493-w

Aleksander T. Szczurek, Emilia Dimitrova, Jessica R. Kelley, Neil P. Blackledge, Robert J. Klose

{"title":"The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription","authors":"Aleksander T. Szczurek, Emilia Dimitrova, Jessica R. Kelley, Neil P. Blackledge, Robert J. Klose","doi":"10.1038/s41556-024-01493-w","DOIUrl":"https://doi.org/10.1038/s41556-024-01493-w","url":null,"abstract":"The Polycomb system has fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here, using rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking, we show how the Polycomb system controls transcription in single cells. We discover that the Polycomb system is not a constitutive block to transcription but instead sustains a long-lived deep promoter OFF state, which limits the frequency with which the promoter can enter into a transcribing state. We demonstrate that Polycomb sustains this deep promoter OFF state by counteracting the binding of factors that enable early transcription pre-initiation complex formation and show that this is necessary for gene repression. Together, these important discoveries provide a rationale for how the Polycomb system controls transcription and suggests a universal mechanism that could enable the Polycomb system to constrain transcription across diverse cellular contexts.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170870","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

Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8+ T cells 氨诱导的溶酶体和线粒体损伤导致效应 CD8+ T 细胞死亡

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01503-x

Huafeng Zhang, Jincheng Liu, Wu Yuan, Qian Zhang, Xiao Luo, Yonggang Li, Yue’e Peng, Jingyu Feng, Xiaoyu Liu, Jie Chen, Yabo Zhou, Jiadi Lv, Nannan Zhou, Jingwei Ma, Ke Tang, Bo Huang

{"title":"Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8+ T cells","authors":"Huafeng Zhang, Jincheng Liu, Wu Yuan, Qian Zhang, Xiao Luo, Yonggang Li, Yue’e Peng, Jingyu Feng, Xiaoyu Liu, Jie Chen, Yabo Zhou, Jiadi Lv, Nannan Zhou, Jingwei Ma, Ke Tang, Bo Huang","doi":"10.1038/s41556-024-01503-x","DOIUrl":"https://doi.org/10.1038/s41556-024-01503-x","url":null,"abstract":"Ammonia is thought to be a cytotoxin and its increase in the blood impairs cell function. However, whether and how this toxin triggers cell death under pathophysiological conditions remains unclear. Here we show that ammonia induces a distinct form of cell death in effector T cells. We found that rapidly proliferating T cells use glutaminolysis to release ammonia in the mitochondria, which is then translocated to and stored in the lysosomes. Excessive ammonia accumulation increases lysosomal pH and results in the termination of lysosomal ammonia storage and ammonia reflux into mitochondria, leading to mitochondrial damage and cell death, which is characterized by lysosomal alkalization, mitochondrial swelling and impaired autophagic flux. Inhibition of glutaminolysis or blocking lysosomal alkalization prevents ammonia-induced T cell death and improves T cell-based antitumour immunotherapy. These findings identify a distinct form of cell death that differs from previously known mechanisms.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170871","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

Inverse blebs operate as hydraulic pumps during mouse blastocyst formation 在小鼠胚泡形成过程中，反向出血作为液压泵起作用

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01501-z

Markus F. Schliffka, Julien G. Dumortier, Diane Pelzer, Arghyadip Mukherjee, Jean-Léon Maître

{"title":"Inverse blebs operate as hydraulic pumps during mouse blastocyst formation","authors":"Markus F. Schliffka, Julien G. Dumortier, Diane Pelzer, Arghyadip Mukherjee, Jean-Léon Maître","doi":"10.1038/s41556-024-01501-z","DOIUrl":"https://doi.org/10.1038/s41556-024-01501-z","url":null,"abstract":"During preimplantation development, mouse embryos form a fluid-filled lumen. Pressurized fluid fractures cell–cell contacts and accumulates into pockets, which coarsen into a single lumen. How the embryo controls intercellular fluid movement during coarsening is unknown. Here we report inverse blebs growing into cells at adhesive contacts. Throughout the embryo we observed hundreds of inverse blebs, each filling with intercellular fluid and retracting within a minute. Inverse blebs grow due to pressure build-up resulting from fluid accumulation and cell–cell adhesion, which locally confines fluid. Inverse blebs retract due to actomyosin contraction, practically pushing fluid within the intercellular space. Importantly, inverse blebs occur infrequently at contacts formed by multiple cells, which effectively serve as fluid sinks. Manipulation of the embryo topology reveals that without sinks inverse blebs pump fluid into one another in futile cycles. We propose that inverse blebs operate as hydraulic pumps to promote luminal coarsening, thereby constituting an instrument used by cells to control fluid movement.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170873","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