Journal of Cell Biology最新文献_第9页

Nuclei as mechanical bumpers during epithelial remodeling. 细胞核是上皮重塑过程中的机械缓冲器

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-26 DOI: 10.1083/jcb.202405078

Noah F de Leeuw,Rashmi Budhathoki,Liam J Russell,Dinah Loerke,J Todd Blankenship

{"title":"Nuclei as mechanical bumpers during epithelial remodeling.","authors":"Noah F de Leeuw,Rashmi Budhathoki,Liam J Russell,Dinah Loerke,J Todd Blankenship","doi":"10.1083/jcb.202405078","DOIUrl":"https://doi.org/10.1083/jcb.202405078","url":null,"abstract":"The morphogenesis of developing tissues relies on extensive cellular rearrangements in shape, position, and identity. A key process in reshaping tissues is cell intercalation-driven elongation, where epithelial cells align and intercalate along a common axis. Typically, analyses focus on how peripheral cortical forces influence cell shape changes. Less attention is given to how inhomogeneities in internal structures, particularly the nucleus, impact cell shaping. Here, we examine how pulsed contractile and extension dynamics interact with the nucleus in elongating Drosophila embryos. Our data show that tightly packed nuclei in apical layers hinder tissue remodeling/oscillatory behaviors. We identify two mechanisms for resolving internuclear tensions: nuclear deformation and dispersion. Embryos with non-deformable nuclei use nuclear dispersion to maintain near-normal extensile rates, while those with non-dispersible nuclei due to microtubule inhibition exhibit disruptions in contractile behaviors. Disrupting both mechanisms leads to severe tissue extension defects and cell extrusion. These findings highlight the critical role of nuclear shape and positioning in topological remodeling of epithelia.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"65 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325113","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

Arf1-dependent LRBA recruitment to Rab4 endosomes is required for endolysosome homeostasis. 内溶酶体稳态需要 Arf1 依赖性 LRBA 招募到 Rab4 内体。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-26 DOI: 10.1083/jcb.202401167

Viktória Szentgyörgyi,Leon Maximilian Lueck,Daan Overwijn,Danilo Ritz,Nadja Zoeller,Alexander Schmidt,Maria Hondele,Anne Spang,Shahrzad Bakhtiar

{"title":"Arf1-dependent LRBA recruitment to Rab4 endosomes is required for endolysosome homeostasis.","authors":"Viktória Szentgyörgyi,Leon Maximilian Lueck,Daan Overwijn,Danilo Ritz,Nadja Zoeller,Alexander Schmidt,Maria Hondele,Anne Spang,Shahrzad Bakhtiar","doi":"10.1083/jcb.202401167","DOIUrl":"https://doi.org/10.1083/jcb.202401167","url":null,"abstract":"Deleterious mutations in the lipopolysaccharide responsive beige-like anchor protein (LRBA) gene cause severe childhood immune dysregulation. The complexity of the symptoms involving multiple organs and the broad range of unpredictable clinical manifestations of LRBA deficiency complicate the choice of therapeutic interventions. Although LRBA has been linked to Rab11-dependent trafficking of the immune checkpoint protein CTLA-4, its precise cellular role remains elusive. We show that LRBA, however, only slightly colocalizes with Rab11. Instead, LRBA is recruited by members of the small GTPase Arf protein family to the TGN and to Rab4+ endosomes, where it controls intracellular traffic. In patient-derived fibroblasts, loss of LRBA led to defects in the endosomal pathway promoting the accumulation of enlarged endolysosomes and lysosome secretion. Thus, LRBA appears to regulate flow through the endosomal system on Rab4+ endosomes. Our data strongly suggest functions of LRBA beyond CTLA-4 trafficking and provide a conceptual framework to develop new therapies for LRBA deficiency.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"9 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325112","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

Claudin 7 suppresses invasion and metastasis through repression of a smooth muscle actin program. Claudin 7通过抑制平滑肌肌动蛋白程序抑制侵袭和转移。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-25 DOI: 10.1083/jcb.202311002

Junior J West,Rosela Golloshi,Chae Yun Cho,Yuqian Wang,Parker Stevenson,Genevieve Stein-O'Brien,Elana J Fertig,Andrew J Ewald

{"title":"Claudin 7 suppresses invasion and metastasis through repression of a smooth muscle actin program.","authors":"Junior J West,Rosela Golloshi,Chae Yun Cho,Yuqian Wang,Parker Stevenson,Genevieve Stein-O'Brien,Elana J Fertig,Andrew J Ewald","doi":"10.1083/jcb.202311002","DOIUrl":"https://doi.org/10.1083/jcb.202311002","url":null,"abstract":"Metastasis initiates when cancer cells escape from the primary tumor, which requires changes to intercellular junctions. Claudins are transmembrane proteins that form the tight junction, and their expression is reduced in aggressive breast tumors. However, claudins' roles during breast cancer metastasis remain unclear. We used gain- and loss-of-function genetics in organoids isolated from murine breast cancer models to establish that Cldn7 suppresses invasion and metastasis. Transcriptomic analysis revealed that Cldn7 knockdown induced smooth muscle actin (SMA)-related genes and a broader mesenchymal phenotype. We validated our results in human cell lines, fresh human tumor tissue, bulk RNA-seq, and public single-cell RNA-seq data. We consistently observed an inverse relationship between Cldn7 expression and expression of SMA-related genes. Furthermore, knockdown and overexpression of SMA-related genes demonstrated that they promote breast cancer invasion. Our data reveal that Cldn7 suppresses breast cancer invasion and metastasis through negative regulation of SMA-related and mesenchymal gene expression.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"216 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321105","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

Forebrain Eml1 depletion reveals early centrosomal dysfunction causing subcortical heterotopia. 前脑 Eml1 缺失揭示了导致皮层下异位的早期中心粒功能障碍。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-24 DOI: 10.1083/jcb.202310157

Donia Zaidi,Kaviya Chinnappa,Berfu Nur Yigit,Valeria Viola,Carmen Cifuentes-Diaz,Ammar Jabali,Ana Uzquiano,Emilie Lemesre,Franck Perez,Julia Ladewig,Julien Ferent,Nurhan Ozlu,Fiona Francis

{"title":"Forebrain Eml1 depletion reveals early centrosomal dysfunction causing subcortical heterotopia.","authors":"Donia Zaidi,Kaviya Chinnappa,Berfu Nur Yigit,Valeria Viola,Carmen Cifuentes-Diaz,Ammar Jabali,Ana Uzquiano,Emilie Lemesre,Franck Perez,Julia Ladewig,Julien Ferent,Nurhan Ozlu,Fiona Francis","doi":"10.1083/jcb.202310157","DOIUrl":"https://doi.org/10.1083/jcb.202310157","url":null,"abstract":"Subcortical heterotopia is a cortical malformation associated with epilepsy, intellectual disability, and an excessive number of cortical neurons in the white matter. Echinoderm microtubule-associated protein like 1 (EML1) mutations lead to subcortical heterotopia, associated with abnormal radial glia positioning in the cortical wall, prior to malformation onset. This perturbed distribution of proliferative cells is likely to be a critical event for heterotopia formation; however, the underlying mechanisms remain unexplained. This study aimed to decipher the early cellular alterations leading to abnormal radial glia. In a forebrain conditional Eml1 mutant model and human patient cells, primary cilia and centrosomes are altered. Microtubule dynamics and cell cycle kinetics are also abnormal in mouse mutant radial glia. By rescuing microtubule formation in Eml1 mutant embryonic brains, abnormal radial glia delamination and heterotopia volume were significantly reduced. Thus, our new model of subcortical heterotopia reveals the causal link between Eml1's function in microtubule regulation and cell position, both critical for correct cortical development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"23 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321085","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

ER-plasma membrane contact sites deliver ER lipids and proteins for rapid cell surface expansion. ER-质膜接触点可输送 ER 脂质和蛋白质，使细胞表面迅速扩张。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-20 DOI: 10.1083/jcb.202308137

Madison Smith,Lincoln Gay,Markus Babst

引用次数: 0

Synaptotagmin-1 in phase: Condensate biology reveals new insights into the synaptic calcium sensor. 相位突触钙敏蛋白-1：凝结生物学揭示突触钙传感器的新见解

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-17 DOI: 10.1083/jcb.202408073

Johannes Vincent Tromm,Dragomir Milovanovic

引用次数: 0

Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8. Migfilin 通过与 SNAP29 和 Vamp8 的直接相互作用促进自噬通量。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-16 DOI: 10.1083/jcb.202312119

Renwei Cai,Panzhu Bai,Meiling Quan,Yanyan Ding,Wenjie Wei,Chengmin Liu,Aihua Yang,Zailin Xiong,Guizhen Li,Binbin Li,Yi Deng,Ruijun Tian,Yan G Zhao,Chuanyue Wu,Ying Sun

{"title":"Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.","authors":"Renwei Cai,Panzhu Bai,Meiling Quan,Yanyan Ding,Wenjie Wei,Chengmin Liu,Aihua Yang,Zailin Xiong,Guizhen Li,Binbin Li,Yi Deng,Ruijun Tian,Yan G Zhao,Chuanyue Wu,Ying Sun","doi":"10.1083/jcb.202312119","DOIUrl":"https://doi.org/10.1083/jcb.202312119","url":null,"abstract":"Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"104 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275162","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

A new player in the biogenesis of lysosome-related organelles. 溶酶体相关细胞器生物生成过程中的新角色。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-11 DOI: 10.1083/jcb.202407194

Anbing Shi

引用次数: 0

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity. TLNRD1 是 CCM 复合物的一个组成部分，能调节内皮屏障的完整性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-09-02 Epub Date: 2024-07-16 DOI: 10.1083/jcb.202310030

Neil J Ball, Sujan Ghimire, Gautier Follain, Ada O Pajari, Diana Wurzinger, Monika Vaitkevičiūtė, Alana R Cowell, Bence Berki, Johanna Ivaska, Ilkka Paatero, Benjamin T Goult, Guillaume Jacquemet

{"title":"TLNRD1 is a CCM complex component and regulates endothelial barrier integrity.","authors":"Neil J Ball, Sujan Ghimire, Gautier Follain, Ada O Pajari, Diana Wurzinger, Monika Vaitkevičiūtė, Alana R Cowell, Bence Berki, Johanna Ivaska, Ilkka Paatero, Benjamin T Goult, Guillaume Jacquemet","doi":"10.1083/jcb.202310030","DOIUrl":"10.1083/jcb.202310030","url":null,"abstract":"We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the four-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity and that the CCM2-TLNRD1 interaction impacts endothelial actin stress fiber and focal adhesion formation. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626834","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

Intraflagellar transport speed is sensitive to genetic and mechanical perturbations to flagellar beating. 鞭毛内运输速度对鞭毛跳动的遗传和机械扰动很敏感。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-09-02 Epub Date: 2024-06-03 DOI: 10.1083/jcb.202401154

Sophie Gray, Cecile Fort, Richard John Wheeler

{"title":"Intraflagellar transport speed is sensitive to genetic and mechanical perturbations to flagellar beating.","authors":"Sophie Gray, Cecile Fort, Richard John Wheeler","doi":"10.1083/jcb.202401154","DOIUrl":"10.1083/jcb.202401154","url":null,"abstract":"Two sets of motor proteins underpin motile cilia/flagella function. The axoneme-associated inner and outer dynein arms drive sliding of adjacent axoneme microtubule doublets to periodically bend the flagellum for beating, while intraflagellar transport (IFT) kinesins and dyneins carry IFT trains bidirectionally along the axoneme. Despite assembling motile cilia and flagella, IFT train speeds have only previously been quantified in immobilized flagella-mechanical immobilization or genetic paralysis. This has limited investigation of the interaction between IFT and flagellar beating. Here, in uniflagellate Leishmania parasites, we use high-frequency, dual-color fluorescence microscopy to visualize IFT train movement in beating flagella. We discovered that adhesion of flagella to a microscope slide is detrimental, reducing IFT train speed and increasing train stalling. In flagella free to move, IFT train speed is not strongly dependent on flagella beat type; however, permanent disruption of flagella beating by deletion of genes necessary for formation or regulation of beating showed an inverse correlation of beat frequency and IFT train speed.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237704","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