Journal of Cell Biology最新文献_第6页

INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis. INPP4B通过PIKfyve和TRPML-1介导的溶酶体外渗促进PDAC的侵袭性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-09 DOI: 10.1083/jcb.202401012

Golam T Saffi, Lydia To, Nicholas Kleine, Ché M P Melo, Keyue Chen, Gizem Genc, K C Daniel Lee, Jonathan Tak-Sum Chow, Gun Ho Jang, Steven Gallinger, Roberto J Botelho, Leonardo Salmena

{"title":"INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.","authors":"Golam T Saffi, Lydia To, Nicholas Kleine, Ché M P Melo, Keyue Chen, Gizem Genc, K C Daniel Lee, Jonathan Tak-Sum Chow, Gun Ho Jang, Steven Gallinger, Roberto J Botelho, Leonardo Salmena","doi":"10.1083/jcb.202401012","DOIUrl":"10.1083/jcb.202401012","url":null,"abstract":"Aggressive solid malignancies, including pancreatic ductal adenocarcinoma (PDAC), can exploit lysosomal exocytosis to modify the tumor microenvironment, enhance motility, and promote invasiveness. However, the molecular pathways through which lysosomal functions are co-opted in malignant cells remain poorly understood. In this study, we demonstrate that inositol polyphosphate 4-phosphatase, Type II (INPP4B) overexpression in PDAC is associated with PDAC progression. We show that INPP4B overexpression promotes peripheral dispersion and exocytosis of lysosomes resulting in increased migratory and invasive potential of PDAC cells. Mechanistically, INPP4B overexpression drives the generation of PtdIns(3,5)P2 on lysosomes in a PIKfyve-dependent manner, which directs TRPML-1 to trigger the release of calcium ions (Ca2+). Our findings offer a molecular understanding of the prognostic significance of INPP4B overexpression in PDAC through the discovery of a novel oncogenic signaling axis that orchestrates migratory and invasive properties of PDAC via the regulation of lysosomal phosphoinositide homeostasis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 11","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906711","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

Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase. 从有丝分裂后期到无丝分裂期，有丝分裂染色体中的核小体浓度接近毫摩尔。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-26 DOI: 10.1083/jcb.202403165

Fernanda Cisneros-Soberanis, Eva L Simpson, Alison J Beckett, Nina Pucekova, Samuel Corless, Natalia Y Kochanova, Ian A Prior, Daniel G Booth, William C Earnshaw

{"title":"Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase.","authors":"Fernanda Cisneros-Soberanis, Eva L Simpson, Alison J Beckett, Nina Pucekova, Samuel Corless, Natalia Y Kochanova, Ian A Prior, Daniel G Booth, William C Earnshaw","doi":"10.1083/jcb.202403165","DOIUrl":"10.1083/jcb.202403165","url":null,"abstract":"Chromosome compaction is a key feature of mitosis and critical for accurate chromosome segregation. However, a precise quantitative analysis of chromosome geometry during mitotic progression is lacking. Here, we use volume electron microscopy to map, with nanometer precision, chromosomes from prometaphase through telophase in human RPE1 cells. During prometaphase, chromosomes acquire a smoother surface, their arms shorten, and the primary centromeric constriction is formed. The chromatin is progressively compacted, ultimately reaching a remarkable nucleosome concentration of over 750 µM in late prometaphase that remains relatively constant during metaphase and early anaphase. Surprisingly, chromosomes then increase their volume in late anaphase prior to deposition of the nuclear envelope. The plateau of total chromosome volume from late prometaphase through early anaphase described here is consistent with proposals that the final stages of chromatin condensation in mitosis involve a limit density, such as might be expected for a process involving phase separation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 11","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055694","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

CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila. CYRI控制果蝇表皮伤口闭合和侵入性边界细胞簇的内聚。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-25 DOI: 10.1083/jcb.202310153

Marvin Rötte,Mila Y Höhne,Dennis Klug,Kirsten Ramlow,Caroline Zedler,Franziska Lehne,Meike Schneider,Maik C Bischoff,Sven Bogdan

{"title":"CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.","authors":"Marvin Rötte,Mila Y Höhne,Dennis Klug,Kirsten Ramlow,Caroline Zedler,Franziska Lehne,Meike Schneider,Maik C Bischoff,Sven Bogdan","doi":"10.1083/jcb.202310153","DOIUrl":"https://doi.org/10.1083/jcb.202310153","url":null,"abstract":"Cell motility is crucial for many biological processes including morphogenesis, wound healing, and cancer invasion. The WAVE regulatory complex (WRC) is a central Arp2/3 regulator driving cell motility downstream of activation by Rac GTPase. CYFIP-related Rac1 interactor (CYRI) proteins are thought to compete with WRC for interaction with Rac1 in a feedback loop regulating lamellipodia dynamics. However, the physiological role of CYRI proteins in vivo in healthy tissues is unclear. Here, we used Drosophila as a model system to study CYRI function at the cellular and organismal levels. We found that CYRI is not only a potent WRC regulator in single macrophages that controls lamellipodial spreading but also identified CYRI as a molecular brake on the Rac-WRC-Arp2/3 pathway to slow down epidermal wound healing. In addition, we found that CYRI limits invasive border cell migration by controlling cluster cohesion and migration. Thus, our data highlight CYRI as an important regulator of cellular and epithelial tissue dynamics conserved across species.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"75 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490567","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

Distinct roles of two homologous kinesins in mammalian motile cilia. 哺乳动物运动纤毛中两种同源驱动蛋白的不同作用

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-24 DOI: 10.1083/jcb.202409214

Kaiming Xu,Ming Li,Guangshuo Ou

引用次数: 0

CryoVesNet: A dedicated framework for synaptic vesicle segmentation in cryo-electron tomograms. CryoVesNet：用于低温电子断层扫描图中突触小泡分割的专用框架。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-24 DOI: 10.1083/jcb.202402169

Amin Khosrozadeh,Raphaela Seeger,Guillaume Witz,Julika Radecke,Jakob B Sørensen,Benoît Zuber

{"title":"CryoVesNet: A dedicated framework for synaptic vesicle segmentation in cryo-electron tomograms.","authors":"Amin Khosrozadeh,Raphaela Seeger,Guillaume Witz,Julika Radecke,Jakob B Sørensen,Benoît Zuber","doi":"10.1083/jcb.202402169","DOIUrl":"https://doi.org/10.1083/jcb.202402169","url":null,"abstract":"Cryo-electron tomography (cryo-ET) has the potential to reveal cell structure down to atomic resolution. Nevertheless, cellular cryo-ET data is highly complex, requiring image segmentation for visualization and quantification of subcellular structures. Due to noise and anisotropic resolution in cryo-ET data, automatic segmentation based on classical computer vision approaches usually does not perform satisfactorily. Communication between neurons relies on neurotransmitter-filled synaptic vesicle (SV) exocytosis. Cryo-ET study of the spatial organization of SVs and their interconnections allows a better understanding of the mechanisms of exocytosis regulation. Accurate SV segmentation is a prerequisite to obtaining a faithful connectivity representation. Hundreds of SVs are present in a synapse, and their manual segmentation is a bottleneck. We addressed this by designing a workflow consisting of a convolutional network followed by post-processing steps. Alongside, we provide an interactive tool for accurately segmenting spherical vesicles. Our pipeline can in principle segment spherical vesicles in any cell type as well as extracellular and in vitro spherical vesicles.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"79 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489668","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

Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation. CTLA4 的快速更替与可逆泛素化的复杂结构有关。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-15 DOI: 10.1083/jcb.202312141

Pei Yee Tey,Almut Dufner,Klaus-Peter Knobeloch,Jonathan N Pruneda,Michael J Clague,Sylvie Urbé

{"title":"Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.","authors":"Pei Yee Tey,Almut Dufner,Klaus-Peter Knobeloch,Jonathan N Pruneda,Michael J Clague,Sylvie Urbé","doi":"10.1083/jcb.202312141","DOIUrl":"https://doi.org/10.1083/jcb.202312141","url":null,"abstract":"The immune checkpoint regulator CTLA4 is an unusually short-lived membrane protein. Here, we show that its lysosomal degradation is dependent on ubiquitylation at lysine residues 203 and 213. Inhibition of the v-ATPase partially restores CTLA4 levels following cycloheximide treatment, but also reveals a fraction that is secreted in exosomes. The endosomal deubiquitylase, USP8, interacts with CTLA4, and its loss enhances CTLA4 ubiquitylation in cancer cells, mouse CD4+ T cells, and cancer cell-derived exosomes. Depletion of the USP8 adapter protein, HD-PTP, but not ESCRT-0 recapitulates this cellular phenotype but shows distinct properties vis-à-vis exosome incorporation. Re-expression of wild-type USP8, but neither a catalytically inactive nor a localization-compromised ΔMIT domain mutant can rescue delayed degradation of CTLA4 or counteract its accumulation in clustered endosomes. UbiCRest analysis of CTLA4-associated ubiquitin chain linkages identifies a complex mixture of conventional Lys63- and more unusual Lys27- and Lys29-linked polyubiquitin chains that may underly the rapidity of protein turnover.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"230 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439232","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

Making lipids very unhappy to discover how they bind to proteins. 让脂质变得非常不开心，以发现它们是如何与蛋白质结合的。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-15 DOI: 10.1083/jcb.202410022

Christopher Stefan,Roberto Covino

引用次数: 0

MONITTR allows real-time imaging of transcription and endogenous proteins in C. elegans. MONITTR 可对秀丽隐杆线虫的转录和内源蛋白进行实时成像。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-14 DOI: 10.1083/jcb.202403198

Xiaofan Liu,Zhi Chang,Pingping Sun,Beibei Cao,Yuzhi Wang,Jie Fang,Yechun Pei,Baohui Chen,Wei Zou

{"title":"MONITTR allows real-time imaging of transcription and endogenous proteins in C. elegans.","authors":"Xiaofan Liu,Zhi Chang,Pingping Sun,Beibei Cao,Yuzhi Wang,Jie Fang,Yechun Pei,Baohui Chen,Wei Zou","doi":"10.1083/jcb.202403198","DOIUrl":"https://doi.org/10.1083/jcb.202403198","url":null,"abstract":"Maximizing cell survival under stress requires rapid and transient adjustments of RNA and protein synthesis. However, capturing these dynamic changes at both single-cell level and across an organism has been challenging. Here, we developed a system named MONITTR (MS2-embedded mCherry-based monitoring of transcription) for real-time simultaneous measurement of nascent transcripts and endogenous protein levels in C. elegans. Utilizing this system, we monitored the transcriptional bursting of fasting-induced genes and found that the epidermis responds to fasting by modulating the proportion of actively transcribing nuclei and transcriptional kinetics of individual alleles. Additionally, our findings revealed the essential roles of the transcription factors NHR-49 and HLH-30 in governing the transcriptional kinetics of fasting-induced genes under fasting. Furthermore, we tracked transcriptional dynamics during heat-shock response and ER unfolded protein response and observed rapid changes in the level of nascent transcripts under stress conditions. Collectively, our study provides a foundation for quantitatively investigating how animals spatiotemporally modulate transcription in various physiological and pathological conditions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"82 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436172","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

Migrasomes: Biogenesis, physiological roles, and therapeutic potentials. 移行体：生物生成、生理作用和治疗潜力。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-14 DOI: 10.1083/jcb.202403051

Haifeng Jiao,Li Yu

引用次数: 0

Fluorescence lifetime sorting reveals tunable enzyme interactions within cytoplasmic condensates. 荧光寿命分选揭示了细胞质凝聚体内可调的酶相互作用。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-14 DOI: 10.1083/jcb.202311105

Leyla E Fahim,Joshua M Marcus,Noah D Powell,Zachary A Ralston,Katherine Walgamotte,Eleonora Perego,Giuseppe Vicidomini,Alessandro Rossetta,Jason E Lee

{"title":"Fluorescence lifetime sorting reveals tunable enzyme interactions within cytoplasmic condensates.","authors":"Leyla E Fahim,Joshua M Marcus,Noah D Powell,Zachary A Ralston,Katherine Walgamotte,Eleonora Perego,Giuseppe Vicidomini,Alessandro Rossetta,Jason E Lee","doi":"10.1083/jcb.202311105","DOIUrl":"https://doi.org/10.1083/jcb.202311105","url":null,"abstract":"Ribonucleoprotein (RNP) condensates partition RNA and protein into multiple liquid phases. The multiphasic feature of condensate-enriched components creates experimental challenges for distinguishing membraneless condensate functions from the surrounding dilute phase. We combined fluorescence lifetime imaging microscopy (FLIM) with phasor plot filtering and segmentation to resolve condensates from the dilute phase. Condensate-specific lifetimes were used to track protein-protein interactions by measuring FLIM-Förster resonance energy transfer (FRET). We used condensate FLIM-FRET to evaluate whether mRNA decapping complex subunits can form decapping-competent interactions within P-bodies. Condensate FLIM-FRET revealed the presence of core subunit interactions within P-bodies under basal conditions and the disruption of interactions between the decapping enzyme (Dcp2) and a critical cofactor (Dcp1A) during oxidative stress. Our results show a context-dependent plasticity of the P-body interaction network, which can be rewired within minutes in response to stimuli. Together, our FLIM-based approaches provide investigators with an automated and rigorous method to uncover and track essential protein-protein interaction dynamics within RNP condensates in live cells.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"56 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436173","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