Journal of Cell Biology最新文献_第2页

Pulling the strings: Contractile VE-cadherin junctions to stabilize angiogenic sprouts. 牵线：收缩ve -钙粘蛋白连接以稳定血管生成芽。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-30 DOI: 10.1083/jcb.202603197

Stephan Huveneers

引用次数: 0

Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling. 巨噬细胞体积的破坏驱动炎症反应和I型干扰素信号传导。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-05-07 DOI: 10.1083/jcb.202411133

James R Cook, Tara A Gleeson, Sara Gago, Stuart M Allan, Kevin N Couper, Catherine B Lawrence, David Brough, Jack P Green

{"title":"Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling.","authors":"James R Cook, Tara A Gleeson, Sara Gago, Stuart M Allan, Kevin N Couper, Catherine B Lawrence, David Brough, Jack P Green","doi":"10.1083/jcb.202411133","DOIUrl":"10.1083/jcb.202411133","url":null,"abstract":"Macrophages coordinate inflammatory and immune responses to threats, yet how they interpret diverse danger signals to tailor inflammation remains unclear. Disturbances in extracellular and intracellular homeostasis alter cell volume, but the consequences for macrophage inflammatory responses are poorly understood. We demonstrate that macrophages use cell volume control as a danger-sensing mechanism to promote and augment inflammation. Using volume-regulated anion channel (VRAC)-deficient macrophages, which lack cell volume control under hypo-osmotic conditions, we show that cell volume disruptions drive transcriptomic reprogramming and induction of inflammation. Cell volume disruption induced type I interferon signaling through a DNA- and TBK1-dependent mechanism, but independent of cGAS and 2'3'-cGAMP transport. VRAC deficiency enhanced macrophage antiviral responses to influenza infection. Cell volume changes synergized with diverse pathogen-associated molecular pattern-mediated signaling to augment type I interferon responses and exacerbate the cytokine storm in mouse models of hyperinflammation. Our findings highlight cell volume as an important regulator in shaping inflammatory responses, expanding our understanding of how macrophages sense complex danger signals.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838260","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

Scrib organizes cortical actomyosin clusters to maintain adherens junctions and angiogenic sprouting. Scrib组织皮层肌动球蛋白簇以维持粘附连接和血管新生发芽。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-27 DOI: 10.1083/jcb.202503146

Lakyn N Mayo, Fiona Duong, Ana Mompeón, Kyle A Jacobs, M Luisa Iruela-Arispe, Matthew L Kutys

{"title":"Scrib organizes cortical actomyosin clusters to maintain adherens junctions and angiogenic sprouting.","authors":"Lakyn N Mayo, Fiona Duong, Ana Mompeón, Kyle A Jacobs, M Luisa Iruela-Arispe, Matthew L Kutys","doi":"10.1083/jcb.202503146","DOIUrl":"https://doi.org/10.1083/jcb.202503146","url":null,"abstract":"Spatiotemporal control of adherens junction fluidity and integrity is critical for angiogenesis, but underlying mechanisms are incompletely understood. To identify unappreciated regulators of endothelial adherens junctions, we performed VE-cadherin proximity ligation mass spectrometry, revealing significant interaction with the multifunctional scaffold Scrib. Utilizing a 3D angiogenesis-on-chip model, we find Scrib-depleted microvessels generate reduced intact sprouts and increased single-cell detachments. This defect was characterized by adherens junction instability and decreased actomyosin in the junctional cortex, yet was not caused by changes in catenin-dependent VE-cadherin coupling to actin. Instead, Scrib controls the formation of cortical actomyosin clusters, which critically organize the architecture and dynamics of the junctional actomyosin cortex to promote adherens junction stability. We further discovered that unconventional myosin-1c is a critical effector linking Scrib cortical dynamics and VE-cadherin to stabilize adherens junctions during angiogenic initiation. Our results demonstrate a new role for Scrib directing cortical actomyosin organization that is critical for precise control of adherens junctions during angiogenesis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772683","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

Phosphatidylserine is a component of the gradient-tracking machine in mating yeast. 磷脂酰丝氨酸是配种酵母梯度跟踪仪的组成部分。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-05-05 DOI: 10.1083/jcb.202504130

Chih-Yu Pai, Xin Wang, Hamida Mahmood, David E Stone

{"title":"Phosphatidylserine is a component of the gradient-tracking machine in mating yeast.","authors":"Chih-Yu Pai, Xin Wang, Hamida Mahmood, David E Stone","doi":"10.1083/jcb.202504130","DOIUrl":"https://doi.org/10.1083/jcb.202504130","url":null,"abstract":"Chemotropism, the ability to orient growth toward external chemical cues, is a fundamental process in diverse eukaryotic systems. During mating, budding yeast cells detect pheromone gradients from potential partners, locating them by assembling a gradient-tracking machine (GTM) at the plasma membrane that redistributes upgradient prior to polarized growth. Although membrane lipids are known to influence pheromone signaling and morphogenesis, their roles in pre-morphogenic gradient tracking have remained unclear. Here, we show that phosphatidylserine (PS), phosphatidylinositol-4,5-bisphosphate, and ergosterol exhibit GTM-like dynamics, polarizing to the default polarity site, redistributing upgradient, and stabilizing at the chemotropic site. Blocking PS synthesis causes a severe and specific gradient-tracking defect, whereas disruption of Bem1 binding to anionic lipids slows but does not abolish tracking. Analysis of polarity, Cdc42 activity, and exocyst dynamics indicates that Bem1 membrane binding contributes to spatial focusing of Cdc42 activation during tracking but cannot account for the pronounced defects caused by PS loss, indicating that PS influences gradient tracking through multiple GTM components. In contrast, ergosterol is dispensable for tracking but required for proper receptor organization and partner alignment after GTM stabilization. Together, these findings establish membrane lipids as integral GTM components and highlight PS as a key regulator of chemotropic gradient sensing through multivalent protein-lipid interactions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838429","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 environmental stress response regulates biophysics of the cytoplasm and survival in quiescence. 环境应激反应调节细胞质的生物物理特性和静止生存。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-30 DOI: 10.1083/jcb.202601119

Lorena Kronig, Carmen A Weber, Pablo Aurelio Gómez-García, Jonas S Fischer, Christian Doerig, Agnès Michel, Paolo Ronchi, Sarah Khawaja, Paola Picotti, Benoît Kornmann, Karsten Weis

{"title":"The environmental stress response regulates biophysics of the cytoplasm and survival in quiescence.","authors":"Lorena Kronig, Carmen A Weber, Pablo Aurelio Gómez-García, Jonas S Fischer, Christian Doerig, Agnès Michel, Paolo Ronchi, Sarah Khawaja, Paola Picotti, Benoît Kornmann, Karsten Weis","doi":"10.1083/jcb.202601119","DOIUrl":"https://doi.org/10.1083/jcb.202601119","url":null,"abstract":"All organisms employ strategies to cope with changing environmental conditions. In budding yeast, nutrient deprivation induces a reversible non-proliferative state known as quiescence, characterized by extensive remodeling of gene expression, metabolism, and cellular biophysical properties. Yeast cells survive prolonged periods of starvation-induced quiescence, provided they can respire in the early stages of glucose withdrawal, and blocking respiration causes premature aging and markedly reduced survival and cytoplasmic diffusion. We find that respiration is required to initiate a quiescence-specific adaptive program. Induction of such a program prior to glucose withdrawal bypasses the need for respiration, rescuing survival and biophysical properties to the levels of respiration-competent cells. This rescue relies on proteomic adaptation and is mediated by Ras/PKA inactivation and Msn2/4-dependent activation of the environmental stress response, leading to modulation of cytoplasmic diffusion. Together, this enables long-term survival in quiescence even in the absence of respiration, underscoring the role of the stress response and the modulation of cytoplasmic properties in quiescence and aging.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772740","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 dynamics of centromere assembly and disassembly during quiescence. 静息期间着丝粒组装和拆卸的动力学。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-09 DOI: 10.1083/jcb.202509067

Océane Marescal, Kuan-Chung Su, Brittania Moodie, Noah J L Taylor, Iain M Cheeseman

{"title":"The dynamics of centromere assembly and disassembly during quiescence.","authors":"Océane Marescal, Kuan-Chung Su, Brittania Moodie, Noah J L Taylor, Iain M Cheeseman","doi":"10.1083/jcb.202509067","DOIUrl":"10.1083/jcb.202509067","url":null,"abstract":"Quiescence is a state in which cells undergo a proliferative arrest while maintaining their capacity to divide again. Here, we analyze how cells regulate their centromeres during quiescence entry and exit. Despite the constitutive localization of centromere proteins in proliferating cells, cells rapidly disassemble most centromere proteins during quiescence entry while preserving those required to maintain centromere identity. We show that this disassembly occurs primarily through the transcriptional downregulation of centromere proteins. During quiescence exit, the centromere is reassembled during the first S phase to regain normal homeostatic centromere protein levels. CENP-A is typically deposited during G1. However, we find that CENP-A deposition does not occur during the G1 immediately following quiescence exit and instead occurs in the G1 after cells complete their first mitosis. We find that the presence of PLK1 distinguishes these distinct G1 states. These findings reveal centromere dynamics during quiescence entry and exit and highlight paradigms for controlling centromere assembly and disassembly.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639006","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

COPI-dependent intra-Golgi recycling at an intermediate stage of cisternal maturation. 在池成熟的中间阶段，copi依赖的高尔基体内循环。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-17 DOI: 10.1083/jcb.202509174

Adam H Krahn, Areti Pantazopoulou, Jotham Austin, Natalie Johnson, Conor F Lee-Smith, Benjamin S Glick

{"title":"COPI-dependent intra-Golgi recycling at an intermediate stage of cisternal maturation.","authors":"Adam H Krahn, Areti Pantazopoulou, Jotham Austin, Natalie Johnson, Conor F Lee-Smith, Benjamin S Glick","doi":"10.1083/jcb.202509174","DOIUrl":"10.1083/jcb.202509174","url":null,"abstract":"The traffic pathways that recycle resident Golgi proteins during cisternal maturation are not completely defined. We addressed this challenge using the yeast Saccharomyces cerevisiae, in which maturation of individual cisternae can be visualized directly. A new assay captures a specific population of Golgi-derived vesicles at the bud neck, thereby revealing which resident Golgi proteins are carried as cargo in those vesicles. This method supplies evidence for at least three classes of intra-Golgi vesicles with different cargo compositions. Consistent with our previously published data, one class of vesicles mediates a late pathway of intra-Golgi recycling with the aid of the AP-1 and Ent5 clathrin adaptors, and a second class of vesicles mediates an early pathway of intra-Golgi recycling with the aid of the COPI vesicle coat. Here, we identify another COPI-dependent pathway of intra-Golgi recycling and show that it operates kinetically between the two previously known pathways. Thus, intra-Golgi recycling is mediated by multiple COPI-dependent pathways followed by a clathrin-dependent pathway.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716733","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

Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis. Hoi1将BLTP2靶向至ER-PM接触位点，调节脂质稳态。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-05-04 Epub Date: 2026-02-26 DOI: 10.1083/jcb.202502131

Samantha K Dziurdzik, Vaishnavi Sridhar, Hailey Eng, Sarah D Neuman, Junran Yan, Michael Davey, Stefan Taubert, Arash Bashirullah, Elizabeth Conibear

{"title":"Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis.","authors":"Samantha K Dziurdzik, Vaishnavi Sridhar, Hailey Eng, Sarah D Neuman, Junran Yan, Michael Davey, Stefan Taubert, Arash Bashirullah, Elizabeth Conibear","doi":"10.1083/jcb.202502131","DOIUrl":"10.1083/jcb.202502131","url":null,"abstract":"Membrane contact sites between organelles are important for maintaining cellular lipid homeostasis. Members of the recently identified family of bridge-like lipid transfer proteins (BLTPs) span apposing membranes at these contact sites to enable the rapid transfer of bulk lipids between organelles. While the VPS13 and ATG2 family members use organelle-specific adaptors for membrane targeting, the mechanisms that regulate other bridge-like transporters are unclear. Here, we identify the conserved protein Ybl086c, which we name Hob interactor 1 (Hoi1), as an adaptor that targets the yeast BLTP2-like proteins Fmp27/Hob1 and Hob2 to ER-plasma membrane (PM) contact sites. Two separate Hoi1 domains interface with α-helical projections that decorate the central hydrophobic channel on Fmp27, and loss of these interactions alters cellular sterol homeostasis. The mutant phenotypes of BLTP2 and HOI1 orthologs indicate these proteins act in a shared pathway in worms and flies. Together, this suggests that Hoi1-mediated recruitment of BLTP2-like proteins represents an evolutionarily conserved mechanism for regulating lipid transport at membrane contact sites.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 5","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289982","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

Actomyosin contractility is a potent suppressor of mesoderm induction by human pluripotent stem cells. 肌动球蛋白收缩性是人类多能干细胞诱导中胚层的有效抑制因子。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-05-04 Epub Date: 2026-04-24 DOI: 10.1083/jcb.202507103

Loic Fort, Vaishna Vamadevan, Wenjun Wang, Ian G Macara

{"title":"Actomyosin contractility is a potent suppressor of mesoderm induction by human pluripotent stem cells.","authors":"Loic Fort, Vaishna Vamadevan, Wenjun Wang, Ian G Macara","doi":"10.1083/jcb.202507103","DOIUrl":"https://doi.org/10.1083/jcb.202507103","url":null,"abstract":"Activation of WNT signaling in human pluripotent stem cells efficiently drives lateral mesoderm specification and subsequent cardiomyocyte differentiation. Stabilization of the WNT effector β-catenin induces mesodermal genes such as TBXT (Brachyury) and triggers an epithelial-mesenchymal transition (EMT). Although mechanical forces are essential for embryonic development, the role of actomyosin contractility during human mesoderm specification remains unclear. We show that increasing contractility through constitutively active Rho kinase or myosin light-chain kinase unexpectedly blocks β-catenin-dependent mesoderm induction and prevents EMT. In contrast, pharmacological or genetic suppression of contractility enhances Brachyury expression and advances EMT onset by 24 h. While β-catenin signaling alone promotes colony-level contractility, we find that contractility must be reduced prior to WNT activation to promote mesoderm specification, indicating a sensitization effect at the pluripotent state. Mechanistically, reduced tension decreases junctional β-catenin and increases nuclear active β-catenin, identifying actomyosin contractility as a key regulator of lineage commitment following WNT pathway activation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 5","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772713","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

Tetraspanin CD82 shapes EGFR signaling outcomes through nanoscale receptor organization. 四跨蛋白CD82通过纳米级受体组织形成EGFR信号转导结果。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-05-04 Epub Date: 2026-03-12 DOI: 10.1083/jcb.202505190

Sebastian Restrepo Cruz, Michael J Wester, Vernon S Pankratz, Diane S Lidke, Keith A Lidke, Jennifer M Gillette

{"title":"Tetraspanin CD82 shapes EGFR signaling outcomes through nanoscale receptor organization.","authors":"Sebastian Restrepo Cruz, Michael J Wester, Vernon S Pankratz, Diane S Lidke, Keith A Lidke, Jennifer M Gillette","doi":"10.1083/jcb.202505190","DOIUrl":"10.1083/jcb.202505190","url":null,"abstract":"Tetraspanins are integral membrane proteins that play a crucial role in organizing and regulating cellular signaling by serving as scaffolds that compartmentalize receptors and other signaling molecules within membrane microdomains. Here, we report how the tetraspanin CD82 modulates the molecular organization and signaling of the EGF receptor (EGFR), a key molecule involved in cellular proliferation, differentiation, and survival. Combining multicolor super-resolution microscopy with advanced image reconstruction and analysis techniques, we demonstrate that CD82 selectively associates with EGFR, promotes receptor oligomerization, and acts as a regulator of ligand-independent receptor phosphorylation in a palmitoylation-dependent manner. Additionally, CD82 promotes a more compact molecular organization of EGFR, which correlates with altered endocytosis and downstream signaling outcomes. These findings underscore the importance of tetraspanins in the spatial and functional regulation of cell surface receptors, with implications for controlling aberrant signaling in disease and positions CD82 as a potential target for developing therapeutic strategies aimed at modulating EGFR signaling by influencing receptor organization.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 5","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432999","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