Journal of Cell Biology最新文献_第8页

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis. 有丝分裂后环状挤出机重建间期基因组结构的定量成像。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-01-09 DOI: 10.1083/jcb.202405169

Andreas Brunner, Natalia Rosalía Morero, Wanlu Zhang, M Julius Hossain, Marko Lampe, Hannah Pflaumer, Aliaksandr Halavatyi, Jan-Michael Peters, Kai S Beckwith, Jan Ellenberg

{"title":"Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.","authors":"Andreas Brunner, Natalia Rosalía Morero, Wanlu Zhang, M Julius Hossain, Marko Lampe, Hannah Pflaumer, Aliaksandr Halavatyi, Jan-Michael Peters, Kai S Beckwith, Jan Ellenberg","doi":"10.1083/jcb.202405169","DOIUrl":"10.1083/jcb.202405169","url":null,"abstract":"How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures. By contrast, the more abundant Cohesin-STAG2 accumulates on chromosomes only gradually later in G1, is responsible for compaction inside TAD structures, and forms paired complexes upon completed nuclear import. Our quantitative time-resolved mapping of mitotic and interphase loop extruders in single cells reveals that the nested loop architecture formed by the sequential action of two Condensins in mitosis is seamlessly replaced by a less compact but conceptually similar hierarchically nested loop architecture driven by the sequential action of two Cohesins.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949410","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}

引用次数: 0

A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes. STING-CASM-GABARAP通路激活溶酶体上的LRRK2。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2025-01-15 DOI: 10.1083/jcb.202310150

Amanda Bentley-DeSousa, Agnes Roczniak-Ferguson, Shawn M Ferguson

引用次数: 0

An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis. eGFP-Col4a2小鼠模型揭示了毛囊形态发生的基底膜动力学。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-10 DOI: 10.1083/jcb.202404003

Duligengaowa Wuergezhen, Eleonore Gindroz, Ritsuko Morita, Kei Hashimoto, Takaya Abe, Hiroshi Kiyonari, Hironobu Fujiwara

{"title":"An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.","authors":"Duligengaowa Wuergezhen, Eleonore Gindroz, Ritsuko Morita, Kei Hashimoto, Takaya Abe, Hiroshi Kiyonari, Hironobu Fujiwara","doi":"10.1083/jcb.202404003","DOIUrl":"10.1083/jcb.202404003","url":null,"abstract":"Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors. Epithelial progenitors are displaced with directionally expanding BMs but do not actively migrate on stationary BM. The addition of a matrix metalloproteinase inhibitor delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Our findings highlight the spatially distinct dynamics of BM and their key roles in orchestrating progenitor cell behavior and organ shape during development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800912","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}

引用次数: 0

Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli. 大肠杆菌中振荡Min系统的生长依赖性浓度梯度。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-02 DOI: 10.1083/jcb.202406107

Claudia Morais Parada, Ching-Cher Sanders Yan, Cheng-Yu Hung, I-Ping Tu, Chao-Ping Hsu, Yu-Ling Shih

{"title":"Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli.","authors":"Claudia Morais Parada, Ching-Cher Sanders Yan, Cheng-Yu Hung, I-Ping Tu, Chao-Ping Hsu, Yu-Ling Shih","doi":"10.1083/jcb.202406107","DOIUrl":"10.1083/jcb.202406107","url":null,"abstract":"Cell division in Escherichia coli is intricately regulated by the MinD and MinE proteins, which form oscillatory waves between cell poles. These waves manifest as concentration gradients that reduce MinC inhibition at the cell center, thereby influencing division site placement. This study explores the plasticity of the MinD gradients resulting from the interdependent interplay between molecular interactions and diffusion in the system. Through live cell imaging, we observed that as cells elongate, the gradient steepens, the midcell concentration decreases, and the oscillation period stabilizes. A one-dimensional model investigates kinetic rate constants representing various molecular interactions, effectively recapitulating our experimental findings. The model reveals the nonlinear dynamics of the system and a dynamic equilibrium among these constants, which underlie variable concentration gradients in growing cells. This study enhances quantitative understanding of MinD oscillations within the cellular environment. Furthermore, it emphasizes the fundamental role of concentration gradients in cellular processes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769243","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}

引用次数: 0

A proteome-wide yeast degron collection for the dynamic study of protein function. 用于蛋白质功能动态研究的蛋白质组范围的酵母degron收集。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-18 DOI: 10.1083/jcb.202409050

Rosario Valenti, Yotam David, Dunya Edilbi, Benjamin Dubreuil, Angela Boshnakovska, Yeynit Asraf, Tomer-Meir Salame, Ehud Sass, Peter Rehling, Maya Schuldiner

{"title":"A proteome-wide yeast degron collection for the dynamic study of protein function.","authors":"Rosario Valenti, Yotam David, Dunya Edilbi, Benjamin Dubreuil, Angela Boshnakovska, Yeynit Asraf, Tomer-Meir Salame, Ehud Sass, Peter Rehling, Maya Schuldiner","doi":"10.1083/jcb.202409050","DOIUrl":"10.1083/jcb.202409050","url":null,"abstract":"Genome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies \"on demand\" protein depletion to overcome these limitations. Here, each protein is tagged with a green fluorescent protein (GFP) and an auxin-inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846662","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}

引用次数: 0

Regulation of Cajal bodies: Unexpected connection to 60S ribosomes. Cajal小体的调控：与60S核糖体的意外联系。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2025-01-09 DOI: 10.1083/jcb.202501009

Edward M C Courvan, Roy R Parker

引用次数: 0

Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation. 非典型CDK6活性通过抑制轴突素多谷氨酰化促进纤毛分解。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-05 DOI: 10.1083/jcb.202405170

Kai He, Xiaobo Sun, Chuan Chen, San Luc, Jielu Hao Robichaud, Yingyi Zhang, Yan Huang, Biyun Ji, Pei-I Ku, Radhika Subramanian, Kun Ling, Jinghua Hu

{"title":"Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation.","authors":"Kai He, Xiaobo Sun, Chuan Chen, San Luc, Jielu Hao Robichaud, Yingyi Zhang, Yan Huang, Biyun Ji, Pei-I Ku, Radhika Subramanian, Kun Ling, Jinghua Hu","doi":"10.1083/jcb.202405170","DOIUrl":"10.1083/jcb.202405170","url":null,"abstract":"Tubulin polyglutamylation is a posttranslational modification that occurs primarily along the axoneme of cilia. Defective axoneme polyglutamylation impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, the precise mechanisms regulating proper axoneme polyglutamylation remain vague. Here, we show that cyclin-dependent kinase 6 (CDK6), but not its paralog CDK4, localizes to the cilia base and suppresses axoneme polyglutamylation by phosphorylating RAB11 family interacting protein 5 (FIP5) at site S641, a critical regulator of cilia import of glutamylases. S641 phosphorylation disrupts the ciliary recruitment of FIP5 and its association with RAB11, thereby reducing the ciliary import of glutamylases. Encouragingly, the FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore cilia function in JBTS cells with defective glutamylation. In summary, our study elucidates the regulatory mechanisms governing axoneme polyglutamylation and suggests that developing CDK6-specific inhibitors could be a promising therapeutic strategy to enhance cilia function in ciliopathy patients.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785848","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}

引用次数: 0

Classical cell cycle kinase limits tubulin polyglutamylation and cilium stability.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2025-01-15 DOI: 10.1083/jcb.202412034

Xiaoliang Liu, Xuecai Ge

引用次数: 0

Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health. 突触破坏：Tau和α-突触核蛋白如何破坏突触健康。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-24 DOI: 10.1083/jcb.202409104

Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman

{"title":"Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.","authors":"Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman","doi":"10.1083/jcb.202409104","DOIUrl":"10.1083/jcb.202409104","url":null,"abstract":"Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's disease (PD), occurring before widespread protein aggregation, neuronal loss, and cognitive decline. While the field has focused on the aggregation of Tau and α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even before their aggregation. Therefore, understanding the mechanisms by which Tau and α-Syn affect presynaptic terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses and potentially halting neurodegeneration. This review focuses on the molecular defects that converge on presynaptic dysfunction caused by Tau and α-Syn. Both proteins have physiological roles in synapses. However, during disease, they acquire abnormal functions due to aberrant interactions and mislocalization. We provide an overview of current research on different essential presynaptic pathways influenced by Tau and α-Syn. Finally, we highlight promising therapeutic targets aimed at maintaining synaptic function in both tauopathies and synucleinopathies.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882093","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}

引用次数: 0

Structural response of microtubule and actin cytoskeletons to direct intracellular load. 微管和肌动蛋白细胞骨架对细胞内直接负荷的结构反应。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-11-15 DOI: 10.1083/jcb.202403136

Ryota Orii, Hirokazu Tanimoto

{"title":"Structural response of microtubule and actin cytoskeletons to direct intracellular load.","authors":"Ryota Orii, Hirokazu Tanimoto","doi":"10.1083/jcb.202403136","DOIUrl":"10.1083/jcb.202403136","url":null,"abstract":"Microtubule and actin are the two major cytoskeletal polymers that form organized functional structures in the interior of eukaryotic cells. Although the structural mechanics of the cytoskeleton has been extensively studied by direct manipulations in in vitro reconstitution systems, such unambiguous characterizations inside the living cell are sparse. Here, we report a comprehensive analysis of how the microtubule and actin cytoskeletons structurally respond to direct intracellular load. Ferrofluid-based intracellular magnetic tweezers reveal rheological properties of the microtubule complex primarily determined by filamentous actin. The strain fields of the microtubule complex and actin meshwork follow the same scaling, suggesting that the two cytoskeletal systems behave as an integrated elastic body. The structural responses of single microtubules to contact and remote forces further evidence that the individual microtubules are enclosed by the elastic medium of actin. These results, directly characterizing the microtubule and actin cytoskeletons as an interacting continuum throughout the cytoplasm, serve as a cornerstone for the physical understanding of intracellular organization.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638716","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}

引用次数: 0