Journal of Cell Biology最新文献_第7页

Kinetochore clustering is mediated by Mps1 phosphorylation of conserved MELT motifs in Stu1. 在Stu1中，着丝粒聚集是由保守的MELT基序的Mps1磷酸化介导的。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-16 DOI: 10.1083/jcb.202601143

Darren R Mallett, Mengqiu Jiang, Gianna M Minnuto, Sue Biggins

引用次数: 0

EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery. EPHA2/ cd44定向运输增强内体渗漏和反义治疗递送。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-11 DOI: 10.1083/jcb.202507217

Sergi Marco, Peter J Walsh, Alexey S Revenko, Tobias Schmidt, Peter A Thomason, Lynn McGarry, A Robert MacLeod, Sonam Ansel, Dina Tataran, Martin Bushell, Chiara Braconi, Jim C Norman

{"title":"EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.","authors":"Sergi Marco, Peter J Walsh, Alexey S Revenko, Tobias Schmidt, Peter A Thomason, Lynn McGarry, A Robert MacLeod, Sonam Ansel, Dina Tataran, Martin Bushell, Chiara Braconi, Jim C Norman","doi":"10.1083/jcb.202507217","DOIUrl":"10.1083/jcb.202507217","url":null,"abstract":"The potential for using therapeutic antisense oligonucleotides (ASOs) has been hampered by a lack of understanding of how they enter cells and subsequently access their targets. Endocytosis contributes to ASO uptake, but the machinery mediating subsequent ASO trafficking to permit suppression of their target mRNAs has not been described. Here, we show that direct ASO engagement with a scavenger receptor (CD44) activates the ERK-RSK axis to promote serine phosphorylation of a receptor tyrosine kinase (EPHA2). Serine phosphorylation of EPHA2 permits endocytosis, trafficking, and accumulation of ASOs in nuclear-captured endosomes. These endosomes are then subject to lipid peroxidation and become leaky, allowing ASOs to escape and effectively suppress target mRNA expression. Inhibition of stress granule-mediated repair of these leaky endosomes further enhances ASO effectiveness. These data identify an endocytic route to the nucleus which may be exploited to maximize the effectiveness of ASO-mediated therapies.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 9","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706639","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

To escape or not to escape, that is the question. 逃还是不逃，这是个问题。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-24 DOI: 10.1083/jcb.202608020

Ya-Cheng Liao, Claudio Bussi

引用次数: 0

PAK4: A vanguard of epithelial vertex remodeling. PAK4：上皮顶点重塑的先锋。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-17 DOI: 10.1083/jcb.202607020

Raghavan Thiagarajan, Jakub Sedzinski

引用次数: 0

PARP1 hyperactivity stalls translation and triggers stress granule formation following DNA damage. PARP1的过度活跃会阻碍翻译并引发DNA损伤后的应激颗粒形成。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-07-29 DOI: 10.1083/jcb.202409149

Maria Tereshchenko, Rebecca Earnshaw, Christopher Chin Sang, Minjung Won, Jeanine L Van Nostrand, Ryan C Russell, Hyun O Lee

{"title":"PARP1 hyperactivity stalls translation and triggers stress granule formation following DNA damage.","authors":"Maria Tereshchenko, Rebecca Earnshaw, Christopher Chin Sang, Minjung Won, Jeanine L Van Nostrand, Ryan C Russell, Hyun O Lee","doi":"10.1083/jcb.202409149","DOIUrl":"https://doi.org/10.1083/jcb.202409149","url":null,"abstract":"Cells respond to various stressors by inhibiting global translation and forming stress granules (SGs), cytoplasmic organelles enriched in certain RNA-binding proteins, and RNA. Genotoxic stress also induces SG assembly, but it is unclear how nuclear stress signals are transmitted to trigger cytoplasmic responses. We show that DNA-damaging agents that activate a nuclear poly(ADP-ribose) polymerase (PARP), PARP1, stall translation and induce SGs. We find that PARP1 activation depletes NAD+, which depletes cellular ATP, activating ATP-sensor AMPK and inhibiting mTORC1 via Raptor phosphorylation. Subsequent hypophosphorylation of 4EBP1 inhibits translation. These effects are suppressed by PAR-metabolism regulators, XRCC1, PARG, and Nudix5, and reversed by NAD+ precursor supplementation. Cells lacking SG scaffolds, G3BP1 and G3BP2, show reduced viability after genotoxic stress, which is rescued by G3BP1 overexpression. These findings link PARP1 activity to translational control and SG formation, which may protect against cell death following DNA damage. These mechanisms provide insight into PARP1- and stress granule-associated diseases, including cancer and neurodegeneration.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619843","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

Design principles of human membrane protein topology. 人体膜蛋白拓扑结构设计原理。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-05-29 DOI: 10.1083/jcb.202604059

Haoxi Wu, Ramanujan S Hegde

引用次数: 0

Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress. 胆固醇生物合成应激下线粒体限制辅酶Q的输出。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-08 DOI: 10.1083/jcb.202507174

Marjana Ndoci, Sharanya Bhattacharya, Ishita Agrawal, Yvonne Hinze, Kathrin Lemke, Anna-Lena Schumacher, Esther Uijttewaal, Ulrich Elling, Steffen Lawo, Patrick Giavalisco, Thomas Langer, Soni Deshwal

{"title":"Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress.","authors":"Marjana Ndoci, Sharanya Bhattacharya, Ishita Agrawal, Yvonne Hinze, Kathrin Lemke, Anna-Lena Schumacher, Esther Uijttewaal, Ulrich Elling, Steffen Lawo, Patrick Giavalisco, Thomas Langer, Soni Deshwal","doi":"10.1083/jcb.202507174","DOIUrl":"10.1083/jcb.202507174","url":null,"abstract":"Coenzyme Q (CoQ) is a hydrophobic lipid primarily synthesized in the mitochondria, though it is also present in non-mitochondrial membranes. However, the metabolic pathways that regulate intracellular CoQ distribution are unknown. This study identifies a key role for the mevalonate pathway in regulating CoQ distribution. The mevalonate pathway synthesizes isopentenyl pyrophosphate (IPP) as the precursor metabolite for both CoQ and cholesterol. We show that CoQ synthesis remains stable regardless of whether the mevalonate pathway is upregulated or downregulated. Upregulation of HMG-CoA reductase (HMGCR), indicative of increased mevalonate flux, enhances cholesterol ester synthesis without altering CoQ levels. When the pathway is downregulated, cholesterol synthesis declines, yet mitochondrial CoQ levels are preserved. Under these limiting conditions, mitochondria reduce CoQ export to maintain their internal CoQ pool. While this adaptation sustains mitochondrial respiration, it diminishes extramitochondrial CoQ availability and sensitizes cells to ferroptosis. These findings uncover a mitochondria-driven mechanism that preserves respiratory function by prioritizing CoQ retention during metabolic stress.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199075","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

Opposing actomyosin pools establish epithelial polarity during naive pluripotency exit. 相反的肌动球蛋白池在初始多能性退出期间建立上皮极性。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-02 DOI: 10.1083/jcb.202408198

Yu Shi, Nadia I Manzi, Nicole R Grater, Nitya Kopparapu, Lauren S Ohler, Bailey N de Jesus, Daniel J Dickinson

{"title":"Opposing actomyosin pools establish epithelial polarity during naive pluripotency exit.","authors":"Yu Shi, Nadia I Manzi, Nicole R Grater, Nitya Kopparapu, Lauren S Ohler, Bailey N de Jesus, Daniel J Dickinson","doi":"10.1083/jcb.202408198","DOIUrl":"10.1083/jcb.202408198","url":null,"abstract":"Epithelial cell polarity is fundamental for embryonic development and organ function. During organogenesis, epithelia often develop from unpolarized precursor cells. How mammalian epithelial cells establish polarity de novo is unclear, in part due to challenges of observing this process in real time in nontransformed cells. Here, we leverage 3D spheroid culture of mouse embryonic stem cells, fluorescent protein knock-in, and live imaging to study epithelial polarity establishment. We show that apical myosin activity, regulated by myosin light chain kinase (MLCK), is crucial for proper epithelial polarity in this system. MLCK-dependent actin flows carry ZO-1, a tight junction component, to the apical junction. A second pool of myosin, regulated by Rho kinase, localizes basally and modulates ZO-1 recruitment to the membrane. MLCK inhibition also disrupts localization of atypical protein kinase C and podocalyxin, supporting a broader role of MLCK-dependent myosin in establishing the apical membrane. Our results support a model in which distinct apical and basal actomyosin pools coordinate epithelial polarity establishment.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149811","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

Centriolar satellites assemble via a hierarchical pathway driven by PCM1 multimerization. 向心卫星通过PCM1多聚化驱动的分层路径组装。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-11 DOI: 10.1083/jcb.202509238

Efe Begar, Ece Seyrek, Selin Yilmaz-Karaoglu, Melis D Arslanhan, Ezgi Odabasi, Elif Nur Firat-Karalar

{"title":"Centriolar satellites assemble via a hierarchical pathway driven by PCM1 multimerization.","authors":"Efe Begar, Ece Seyrek, Selin Yilmaz-Karaoglu, Melis D Arslanhan, Ezgi Odabasi, Elif Nur Firat-Karalar","doi":"10.1083/jcb.202509238","DOIUrl":"10.1083/jcb.202509238","url":null,"abstract":"Centriolar satellites (CS) are ubiquitous membraneless organelles with diverse functions and links to developmental and neuronal diseases. However, the molecular principles governing their assembly and regulation remain poorly understood. To address this, we developed cellular and in vitro biogenesis assays that enable spatiotemporal quantification of CS granule properties during assembly, remodeling, and maintenance. Using these tools, we show that CS assemble via a hierarchical pathway initiated by pericentriolar material-1 (PCM1) scaffold formation and followed by client recruitment. PCM1 intrinsically assembles into granules through multimerization, a process modulated by the cytoskeleton. High-resolution imaging revealed that PCM1 and its clients occupy distinct subdomains with different compositions and dynamics. Perturbing PCM1 multimerization impaired ciliary signaling and mitotic progression, underscoring its functional importance. Together, these findings define the molecular basis of CS biogenesis, establish tools to probe CS regulation, and provide a framework for understanding how CS deregulation contributes to disease. More broadly, these may extend to other membraneless organelles and help explain their specificity and plasticity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217473","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

The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation. Rab GEF VINE将磷酸酶募集与gap介导的Rab5失活结合起来。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-07-07 DOI: 10.1083/jcb.202601107

Mia S Frier, Shawn P Shortill, Michael Davey, Elizabeth Conibear

{"title":"The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation.","authors":"Mia S Frier, Shawn P Shortill, Michael Davey, Elizabeth Conibear","doi":"10.1083/jcb.202601107","DOIUrl":"10.1083/jcb.202601107","url":null,"abstract":"Rab5-family GTPases cycle between active and inactive forms to regulate endosomal membrane identity and protein trafficking. VPS9-family guanine nucleotide exchange factors (GEFs) promote Rab activation at endosomes, whereas GTPase-activating proteins (GAPs) oppose Rab signaling. Here, we identify an unexpected role for the yeast VPS9-family GEF complex VINE in promoting the inactivation of the Rab5 homolog Vps21. Through genome-wide proximity screening, predictive modeling, targeted mutagenesis, and in vivo assays, we show that VINE recruits the protein phosphatase Glc7 through the ankyrin repeat-containing domain of its GEF subunit Vrl1. Our results suggest this directs the dephosphorylation of Kxd1, a subunit of the GAP adaptor BLOC-1, which in turn enhances its interaction with the Vps21-specific GAP Msb3 and accelerates GAP-mediated Vps21 inactivation. Thus, VINE is a VPS9-family GEF complex that selectively limits endosomal Rab signaling. These findings reveal a novel mechanism integrating positive and negative Rab regulation, providing insight into how Rab5 signaling is fine-tuned during endosomal trafficking and maturation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396636","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