Journal of Cell Biology最新文献_第6页

Rhomboid protease Rhbdl2 influences macrophage recruitment and wound repair in zebrafish 菱形蛋白酶Rhbdl2影响斑马鱼巨噬细胞募集和伤口修复

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2026-09-11 DOI: 10.1083/jcb.202602106

Saroj Gourkanti,Gayathri Ramakrishnan,Jacqueline Cheung,Taylor J. Schoen,Yazmin Munoz,Rosa M. Chavez,Jan Dohnálek,Katie Martin,Matthew Lovett-Barron,Thomas Whisenant,Kvido Strisovsky,Sonya E. Neal

{"title":"Rhomboid protease Rhbdl2 influences macrophage recruitment and wound repair in zebrafish","authors":"Saroj Gourkanti,Gayathri Ramakrishnan,Jacqueline Cheung,Taylor J. Schoen,Yazmin Munoz,Rosa M. Chavez,Jan Dohnálek,Katie Martin,Matthew Lovett-Barron,Thomas Whisenant,Kvido Strisovsky,Sonya E. Neal","doi":"10.1083/jcb.202602106","DOIUrl":"https://doi.org/10.1083/jcb.202602106","url":null,"abstract":"Wound repair requires tight control of immune cell behavior, yet the mechanisms that restrain immune-driven wound repair responses remain poorly defined. Here, we demonstrate that rhomboid intramembrane serine protease Rhbdl2 influences wound repair in zebrafish. We generated rhbdl2 mutants using CRISPR-Cas9 and found that, although Rhbdl2 is dispensable for normal development, its loss triggers enhanced wound repair following injury. This regenerative phenotype is accompanied by increased macrophage migration speed and accumulation at the wound site, as well as elevated early apoptosis and cell proliferation. Proteomic analyses reveal increased Rac2 protein levels in rhbdl2 mutants, which was previously identified as a regulator of leukocyte motility. Functionally, Rac2 morpholino–mediated knockdown in rhbdl2 mutant larvae suppresses the elevated macrophage recruitment and enhanced tissue repair phenotype. Together, these findings identify Rhbdl2 as a modulator of macrophage recruitment to the wound site during tissue repair, with implications for inflammatory disease, fibrosis, and tumor–immune interactions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"7 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148932596","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

Rhoptry biogenesis in Plasmodium sporozoites is uncoupled from mitosis and forms distinct pairs. 疟原虫孢子体的虫体生物发生与有丝分裂分离，形成不同的成对。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-03 DOI: 10.1083/jcb.202602062

Benjamin Liffner, Thiago Luiz Alves E Silva, Elizabeth Glennon, Veronica Primavera, Elaine Hoffman, Leonhard Satrio Arinanto, Geoffrey I McFadden, Christopher D Goodman, Igor Blatov, Declan Brady, Rita Tewari, Alexandre Fernandes, Ana Parreira, Maria M Mota, Alexis Kaushansky, Joel Vega-Rodriguez, Sabrina Absalon

{"title":"Rhoptry biogenesis in Plasmodium sporozoites is uncoupled from mitosis and forms distinct pairs.","authors":"Benjamin Liffner, Thiago Luiz Alves E Silva, Elizabeth Glennon, Veronica Primavera, Elaine Hoffman, Leonhard Satrio Arinanto, Geoffrey I McFadden, Christopher D Goodman, Igor Blatov, Declan Brady, Rita Tewari, Alexandre Fernandes, Ana Parreira, Maria M Mota, Alexis Kaushansky, Joel Vega-Rodriguez, Sabrina Absalon","doi":"10.1083/jcb.202602062","DOIUrl":"https://doi.org/10.1083/jcb.202602062","url":null,"abstract":"Malaria transmission relies on sporozoite formation in the mosquito midgut and subsequent salivary gland (SG) invasion. Despite their importance, the cell biology of these processes remains poorly understood. We apply mosquito tissue ultrastructure expansion microscopy (MoTissU-ExM), which physically expands infected mosquito tissues while preserving host and parasite ultrastructure. MoTissU-ExM reveals parasite structures and organelles, including features previously seen only by electron microscopy and novel structures not observed before. We use MoTissU-ExM to investigate sporozoite formation and SG invasion, focusing on rhoptries-secretory organelles critical for host cell invasion. We establish a timeline for rhoptry biogenesis, show that two rhoptries are consumed during SG invasion, and provide the first evidence that rhoptry pairs are specialized for different invasion events. We further characterize RON11 as the first protein involved in sporozoite rhoptry biogenesis; its disruption produces sporozoites that specifically fail to invade SG epithelial cells, blocking parasite transmission.","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663972","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

GCL pruning of PIP3 establishes the soma-germline boundary. PIP3的GCL剪枝建立了体细胞-种系的边界。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-22 DOI: 10.1083/jcb.202604036

Mariyah Saiduddin, Juhee Pae, Asier M Marcos-Vidal, Martin L Alani, Ruth Lehmann

{"title":"GCL pruning of PIP3 establishes the soma-germline boundary.","authors":"Mariyah Saiduddin, Juhee Pae, Asier M Marcos-Vidal, Martin L Alani, Ruth Lehmann","doi":"10.1083/jcb.202604036","DOIUrl":"10.1083/jcb.202604036","url":null,"abstract":"Primordial germ cells (PGCs) are the first cells specified in the Drosophila embryo and are precursors to the germline. Their formation requires suppression of somatic fates, achieved by degrading the receptor tyrosine kinase Torso at the posterior pole through the ubiquitin ligase adaptor germ cell-less (GCL). Although Torso is known to antagonize PGC formation, the underlying mechanisms remained unclear. Here, we combine optogenetic Ras activation and Ras effector loop mutants to show that Ras suppresses PGC formation independently of the canonical Raf/MEK/ERK pathway. We identify an unexpected early role for Torso in activating phosphoinositide 3-kinase (PI3K), generating membrane domains enriched in phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Elevated PI3K activity disrupts PGC formation, while reduced PI3K activity creates ectopic PGCs. We demonstrate that GCL remodels the posterior pole membrane by suppressing Torso-dependent PI3K activation. Clearing PIP3 enables myosin II enrichment, allowing for PGC formation. Together, our findings reveal how antagonistic Torso and GCL activities establish the soma-germline boundary by organizing cortical lipids.","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/PMC13390627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549125","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

Spatiotemporal regulation of DNA repair proteins between Golgi and nucleus maintains genome stability. 高尔基体与细胞核间DNA修复蛋白的时空调控维持了基因组的稳定性。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-28 DOI: 10.1083/jcb.202605024

George Galea, Karolina Kuodyte, Muzamil Majid Khan, Peter J Thul, Beate Neumann, Emma Lundberg, Rainer Pepperkok

{"title":"Spatiotemporal regulation of DNA repair proteins between Golgi and nucleus maintains genome stability.","authors":"George Galea, Karolina Kuodyte, Muzamil Majid Khan, Peter J Thul, Beate Neumann, Emma Lundberg, Rainer Pepperkok","doi":"10.1083/jcb.202605024","DOIUrl":"10.1083/jcb.202605024","url":null,"abstract":"The Golgi complex serves as a critical hub for cellular homeostasis, yet its communication with the nucleus remains largely unexplored. By analyzing and siRNA-validating localization data from the Human Protein Atlas, we uncovered substantial proteome interconnectivity between the Golgi and nucleus, including an unexpected enrichment for DNA repair factors. We identify a cluster of DNA damage response (DDR) proteins occupying distinct sub-Golgi compartments that redistribute dynamically between the Golgi and nucleus in response to genotoxic stress, with the type of DNA lesion shaping the direction of redistribution. Focusing on the homologous recombination (HR) regulator RAD51C, we show that DNA damage triggers ataxia telangiectasia mutated (ATM)-dependent release of a giantin-tethered Golgi RAD51C pool, with subsequent importin-β-dependent nuclear import, where repair-associated foci form. Giantin depletion prematurely releases RAD51C, producing aberrant nuclear foci lacking key DDR markers, reducing ATM activation and HR efficiency, elevating genome instability, and accelerating proliferation. The Golgi thus acts as a spatiotemporal coordination node for DDR factors safeguarding genomic stability.","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/PMC13411647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603385","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

CENP-C in two acts: Dynamic roles in male meiotic centromere assembly. CENP-C在雄性减数分裂着丝粒组装中的动态作用。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-25 DOI: 10.1083/jcb.202607032

Analise D Coon, Arunika Das

引用次数: 0

PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function. PAK4促进顶点重塑以维持上皮完整性和屏障功能。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-20 DOI: 10.1083/jcb.202510024

Babli Adhikary, Alexander Chang, Atsuko Y Higashi, Hideki Chiba, Ann L Miller, Tomohito Higashi

{"title":"PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function.","authors":"Babli Adhikary, Alexander Chang, Atsuko Y Higashi, Hideki Chiba, Ann L Miller, Tomohito Higashi","doi":"10.1083/jcb.202510024","DOIUrl":"10.1083/jcb.202510024","url":null,"abstract":"Cell-cell junctions are essential for epithelial integrity and barrier function, but the mechanisms regulating their remodeling remain unclear. Here, we investigated the role of the junctional kinase PAK4 in vertex remodeling. PAK4 accumulated at multicellular vertices in MDCK cells and Xenopus embryos. Inhibition or knockout (KO) of PAK4 increased the number of higher-order vertices, caused junctional discontinuities, and impaired barrier function in MDCK cells. PAK4 recruitment required the scaffolding protein Afadin. Severe junctional defects and reduced barrier function in Afdn-KO cells were partially rescued by artificial PAK4 targeting. In Xenopus embryos, PAK4 showed dynamic accumulation at remodeling vertices, and PAK4 inhibition hindered vertex remodeling. Expression of an amino-terminal fragment (PAK4-NT) impaired remodeling, induced cytokinetic failure, and caused barrier leakage at multicellular vertices. In both systems, PAK4-deficient cells exhibited abnormal accumulation of junctional myosin II, likely due to reduced myosin phosphatase activity. These findings indicate that PAK4 and Afadin cooperate to maintain epithelial integrity and barrier function by promoting vertex remodeling.","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520560","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

STAT5A-α-actinin axis links actin integrity to mitochondrial homeostasis and innate immune activation. STAT5A-α-肌动蛋白轴将肌动蛋白完整性与线粒体稳态和先天免疫激活联系起来。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-07 DOI: 10.1083/jcb.202601131

Boyue Sun, Mathumathi Krishnamohan, Reinat Nevo, Eyal Zoler, Yael Elbaz-Alon, Benjamin Geiger, Gideon Schreiber

{"title":"STAT5A-α-actinin axis links actin integrity to mitochondrial homeostasis and innate immune activation.","authors":"Boyue Sun, Mathumathi Krishnamohan, Reinat Nevo, Eyal Zoler, Yael Elbaz-Alon, Benjamin Geiger, Gideon Schreiber","doi":"10.1083/jcb.202601131","DOIUrl":"https://doi.org/10.1083/jcb.202601131","url":null,"abstract":"STAT5A is unique in its diverse expression in different cells. Here, we show that STAT5A deficiency results in reduced expression of the actin-bundling protein α-actinin-1, which alters cytoskeletal reorganization, including loss of actin bundles, reduction of cellular motility, and clustering of mitochondria and endoplasmic reticulum in the perinuclear region. These changes in cellular architecture led to production of ROS by the mitochondria, which may be explained by reduced peroxisome abundance. This, in turn, results in dsDNA breaks and formation of cytoplasmic micronuclei, and activating the cGAS-STING pathway, and mediating type I IFN production and the expression of IFN-stimulated genes. The ectopic expression of α-actinin-1 or STAT5A in STAT5A knockout cells is sufficient to restore actin bundle formation and nullifies all downstream effects. Conversely, inhibiting downstream steps suppresses only subsequent events in the pathway. STAT5A knockout results in a similar phenotype as seen with cytochalasin B, an inhibitor of actin polymerization. Overall, we show that STAT5A-α-actinin-1 links cytoskeleton integrity to mitochondrial immune regulation.","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684547","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

Nanoscale junctional membrane curvatures recruit BIN1 and SNX9 for endothelial collective migration. 纳米级连接膜曲率使BIN1和SNX9参与内皮细胞的集体迁移。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-27 DOI: 10.1083/jcb.202509207

Vera Janssen, Hannah de Kraker, Jesse S Aaron, Annett de Haan, Iris de Heer, Satya Khuon, Jason Da Silva, Amber J M Driessen, Teng-Leong Chew, Josephine M E Tan, Anne K Lagendijk, Ana Angulo-Urarte, Stephan Huveneers

{"title":"Nanoscale junctional membrane curvatures recruit BIN1 and SNX9 for endothelial collective migration.","authors":"Vera Janssen, Hannah de Kraker, Jesse S Aaron, Annett de Haan, Iris de Heer, Satya Khuon, Jason Da Silva, Amber J M Driessen, Teng-Leong Chew, Josephine M E Tan, Anne K Lagendijk, Ana Angulo-Urarte, Stephan Huveneers","doi":"10.1083/jcb.202509207","DOIUrl":"10.1083/jcb.202509207","url":null,"abstract":"Collective endothelial migration during vascular development relies on dynamic cell-cell contacts, yet how the junctions between leader and follower cells are organized remains poorly understood. Using Cryo-SIM followed by FIB-SEM, we investigated the nanoscale 3D ultrastructure of asymmetric adherens junctions (AAJs), revealing a wide spectrum of membrane folds at the contact interface between migrating endothelial cells. By performing a junction localization screen, we identified a variety of membrane curvature-sensing BAR domain proteins selectively enriched at AAJs. Among these, BIN1 and SNX9 emerged as novel regulators of front-to-rear polarity in follower cells during endothelial collective migration. The spatiotemporal recruitment of these individual BAR proteins associated with distinct phases of AAJ remodeling. Furthermore, depletion of SNX9 disturbed VE-cadherin dynamics, endothelial cell directionality, and sheet migration in the common cardinal vein of zebrafish. These findings highlight junctional nanoscale membrane curvatures as hubs for the spatiotemporal recruitment of a repertoire of BAR proteins to remodel AAJs and guide collective endothelial migration during vascular development.","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/PMC13404086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591526","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

CAST/ELKS-endophilin-A interaction ensures synaptic vesicle pool size. CAST/ elks -内啡肽- a相互作用确保突触囊泡池大小。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-07-22 DOI: 10.1083/jcb.202508077

Yasunori Mori, Hirokazu Sakamoto, Yeon-Jeong Kim, Shun Hamada, Fumihiro Kaku, Yamato Hida, Kenzo Hirose, Toshihisa Ohtsuka

{"title":"CAST/ELKS-endophilin-A interaction ensures synaptic vesicle pool size.","authors":"Yasunori Mori, Hirokazu Sakamoto, Yeon-Jeong Kim, Shun Hamada, Fumihiro Kaku, Yamato Hida, Kenzo Hirose, Toshihisa Ohtsuka","doi":"10.1083/jcb.202508077","DOIUrl":"10.1083/jcb.202508077","url":null,"abstract":"Efficient neurotransmission relies on the precise integration of synaptic vesicle (SV) recycling at the presynaptic terminal. While SV recycling is essential for neurotransmission, the molecular mechanisms coordinating vesicle dynamics at presynaptic terminals remain poorly understood. Here we report that the active zone proteins, CAST and ELKS, play a crucial role in maintaining functional SV pool size through direct interaction with endophilin-A family proteins. In cultured hippocampal neurons, disruption of CAST binding to endophilin-A resulted in a reduced number of SVs available for release, mislocalization of endophilin-A, and altered presynaptic localization of clathrin light chain. Furthermore, reduction of endophilin-A affected expression levels of active zone proteins. Collectively, these findings redefine the role of CAST/ELKS beyond active zone structural organization, demonstrating that their interaction with endophilin-A contributes to maintaining the SV pool required for sustained synaptic transmission at the presynaptic active zone.","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/PMC13390633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549143","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

Tunnel traffic: Import stress induces bidirectional mitochondrial transfer between cells. 隧道交通：输入压力诱导细胞间双向线粒体转移。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-09-07 Epub Date: 2026-08-13 DOI: 10.1083/jcb.202607143

Konstanze F Winklhofer, Johannes M Herrmann

引用次数: 0