Journal of cell science最新文献_第2页

Disordered hinge regions of the AP-3 adaptor complex promote vesicle budding from the late Golgi in yeast. AP-3适配体复合物的无序铰链区可促进酵母中囊泡从晚期高尔基体出芽。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-11-01 Epub Date: 2024-11-08 DOI: 10.1242/jcs.262234

Mitchell Leih, Rachael L Plemel, Matt West, Cortney G Angers, Alexey J Merz, Greg Odorizzi

{"title":"Disordered hinge regions of the AP-3 adaptor complex promote vesicle budding from the late Golgi in yeast.","authors":"Mitchell Leih, Rachael L Plemel, Matt West, Cortney G Angers, Alexey J Merz, Greg Odorizzi","doi":"10.1242/jcs.262234","DOIUrl":"10.1242/jcs.262234","url":null,"abstract":"Vesicles bud from maturing Golgi cisternae in a programmed sequence. Budding is mediated by adaptors that recruit cargoes and facilitate vesicle biogenesis. In Saccharomyces cerevisiae, the AP-3 adaptor complex directs cargoes from the Golgi to the lysosomal vacuole. The AP-3 core consists of small and medium subunits complexed with two non-identical large subunits, β3 (Apl6) and δ (Apl5). The C-termini of β3 and δ were thought to be flexible hinges linking the core to ear domains that bind accessory proteins involved in vesicular transport. We found by computational modeling that the yeast β3 and δ hinges are intrinsically disordered and lack folded ear domains. When either hinge is truncated, AP-3 is recruited to the Golgi, but vesicle budding is impaired and cargoes normally sorted into the AP-3 pathway are mistargeted. This budding deficiency causes AP-3 to accumulate on ring-like Golgi structures adjacent to GGA adaptors that, in wild-type cells, bud vesicles downstream of AP-3 during Golgi maturation. Thus, each of the disordered hinges of yeast AP-3 has a crucial role in mediating transport vesicle formation at the Golgi.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Graham A. Dunn (1944-2024) - a pioneer of cell migration analysis. 格雷厄姆-邓恩（Graham A. Dunn，1944-2024 年）--细胞迁移分析的先驱。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-11-01 Epub Date: 2024-11-07 DOI: 10.1242/jcs.263606

Gareth E Jones, Alexander Bershadsky

引用次数: 0

Spatiotemporal regulation of organelle transport by spindle position checkpoint kinase Kin4. 纺锤体位置检查点激酶Kin4对细胞器运输的时空调控

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 10.1242/jcs.261948

Lakhan Ekal, Abdulaziz M S Alqahtani, Kathryn R Ayscough, Ewald H Hettema

引用次数: 0

An image-based RNAi screen identifies the EGF.R signaling pathway as a regulator of Imp/ IGF2BP RNP granules. 基于图像的 RNAi 筛选确定 EGF.R 信号通路是 Imp/ IGF2BP RNP 颗粒的调节因子。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-31 DOI: 10.1242/jcs.262119

Fabienne De Graeve, Eric Debreuve, Kavya Vinayan Pushpalata, Xuchun Zhang, Somia Rahmoun, Djampa Kozlowski, Nicholas Cedilnik, Jeshlee Vijayakumar, Paul Cassini, Sebastien Schaub, Xavier Descombes, Florence Besse

{"title":"An image-based RNAi screen identifies the EGF.R signaling pathway as a regulator of Imp/ IGF2BP RNP granules.","authors":"Fabienne De Graeve, Eric Debreuve, Kavya Vinayan Pushpalata, Xuchun Zhang, Somia Rahmoun, Djampa Kozlowski, Nicholas Cedilnik, Jeshlee Vijayakumar, Paul Cassini, Sebastien Schaub, Xavier Descombes, Florence Besse","doi":"10.1242/jcs.262119","DOIUrl":"https://doi.org/10.1242/jcs.262119","url":null,"abstract":"Biomolecular condensates have recently retained much attention since they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic RNP granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatio-temporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly. The signaling pathways controlling this process in a cellular context are however still largely unknown. Here, we aimed at identifying regulators of cytoplasmic RNP granules characterized by the presence of the evolutionarily conserved IGF2BP/Imp/ZBP1 RNA binding protein. We performed a high-content image-based RNAi screen targeting all Drosophila genes encoding RNA binding proteins, phosphatases and kinases. This led to the identification of dozens of genes regulating the number of Imp+ RNP granules in S2R+ cells, among which components of the MAPK pathway. Combining functional approaches, phospho-mapping and generation of phospho-variants, we further showed that the EGF.R signaling inhibits Imp+ RNP granule assembly through activation of MAPK/Rolled and Imp S15 phosphosite. This work illustrates how signaling pathways can regulate cellular condensate assembly by post-translational modifications of specific components.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

CAMSAP3 forms dimers via its α-helix domain that directly stabilize non-centrosomal microtubule minus ends. CAMSAP3 通过其 α-helix 结构域形成二聚体，直接稳定非中心粒微管负端。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-31 DOI: 10.1242/jcs.263609

Yuejia Li, Rui Zhang, Jinqi Ren, Wei Chen, Zhengrong Zhou, Honglin Xu, Dong Li, Haisu Cheng, Qi Xie, Wei Ji, Wei Feng, Xin Liang, Wenxiang Meng

{"title":"CAMSAP3 forms dimers via its α-helix domain that directly stabilize non-centrosomal microtubule minus ends.","authors":"Yuejia Li, Rui Zhang, Jinqi Ren, Wei Chen, Zhengrong Zhou, Honglin Xu, Dong Li, Haisu Cheng, Qi Xie, Wei Ji, Wei Feng, Xin Liang, Wenxiang Meng","doi":"10.1242/jcs.263609","DOIUrl":"10.1242/jcs.263609","url":null,"abstract":"Microtubules are vital components of the cytoskeleton. Their plus ends are dynamic and respond to changes in cell morphology, while the minus ends are stable and serve a crucial role in microtubule seeding and maintaining spatial organization. In mammalian cells, the calmodulin-regulated spectrin-associated proteins (CAMSAPs), play a key role in directly regulating the dynamics of non-centrosomal microtubules minus ends. However, the molecular mechanisms are not yet fully understood. Our study reveals that CAMSAP3 forms dimers through its C-terminal α-helix; this dimerization not only enhances the microtubule-binding affinity of the CKK domain but also enables the CKK domain to regulate the dynamics of microtubules. Furthermore, CAMSAP3 also specializes in decorating at the minus end of microtubules through the combined action of the microtubule-binding domain (MBD) and the C-terminal α-helix, thereby achieving dynamic regulation of the minus ends of microtubules. These findings are crucial for advancing our understanding and treatment of diseases associated with non-centrosomal microtubules.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules. 线粒体未折叠蛋白反应的激活调节应激颗粒的动态形成。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-28 DOI: 10.1242/jcs.263548

Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker

{"title":"Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules.","authors":"Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker","doi":"10.1242/jcs.263548","DOIUrl":"https://doi.org/10.1242/jcs.263548","url":null,"abstract":"To rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that SGs and UPRmt pathways are intertwined and communicate. UPRmt induction results in eIF2a phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. The induction of GADD34 during late UPRmt protects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial functions and cellular survival are enhanced during UPRmt activation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmt that may contribute to restoring mitochondrial functions under stressful conditions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Chemomechanical regulation of EZH2 localization controls epithelial-mesenchymal transition. EZH2定位的化学机械调控控制着上皮-间质转化。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-25 DOI: 10.1242/jcs.262190

Jessica L Sacco, Zachary T Vaneman, Ava Self, Elix Sumner, Stella Kibinda, Chinmay S Sankhe, Esther W Gomez

{"title":"Chemomechanical regulation of EZH2 localization controls epithelial-mesenchymal transition.","authors":"Jessica L Sacco, Zachary T Vaneman, Ava Self, Elix Sumner, Stella Kibinda, Chinmay S Sankhe, Esther W Gomez","doi":"10.1242/jcs.262190","DOIUrl":"https://doi.org/10.1242/jcs.262190","url":null,"abstract":"The methyltransferase enhancer of zeste homolog 2 (EZH2) regulates gene expression and aberrant EZH2 expression and signaling can drive fibrosis and cancer. However, it is not clear how chemical and mechanical signals are integrated to regulate EZH2 and gene expression. We show that culture of cells on stiff matrices in concert with transforming growth factor (TGF)-β1 promotes nuclear localization of EZH2 and an increase in the levels of the corresponding histone modification, H3K27me3, thereby regulating gene expression. EZH2 activity and expression are required for TGFβ1- and stiffness-induced increases in H3K27me3 levels as well as for morphological and gene expression changes associated with epithelial-mesenchymal transition (EMT). Inhibition of Rho associated kinase (ROCK) or myosin II signaling attenuates TGFβ1-induced nuclear localization of EZH2 and decreases H3K27me3 levels in cells cultured on stiff substrata, suggesting that cellular contractility, in concert with a major cancer signaling regulator TGFβ1, modulates EZH2 subcellular localization. These findings provide a contractility-dependent mechanism by which matrix stiffness and TGFβ1 together mediate EZH2 signaling to promote EMT.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis. 果蝇 Canoe 的双 Ras 关联（RA）域在形态发生过程中连接细胞连接和细胞骨架方面具有不同的作用。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-25 DOI: 10.1242/jcs.263546

Emily D McParland, Noah J Gurley, Leah R Wolfsberg, T Amber Butcher, Abhi Bhattarai, Corbin C Jensen, Ruth I Johnson, Kevin C Slep, Mark Peifer

{"title":"The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis.","authors":"Emily D McParland, Noah J Gurley, Leah R Wolfsberg, T Amber Butcher, Abhi Bhattarai, Corbin C Jensen, Ruth I Johnson, Kevin C Slep, Mark Peifer","doi":"10.1242/jcs.263546","DOIUrl":"https://doi.org/10.1242/jcs.263546","url":null,"abstract":"During development cells must change shape and move without disrupting dynamic tissue architecture. This requires robust linkage of cell-cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian Afadin play key roles. One central task for the field is defining mechanisms by which upstream inputs from Ras-family GTPases regulate Canoe/Afadin. They are unusual in sharing two tandem Ras-association (RA) domains, which, when deleted, virtually eliminate Canoe function. Work in vitro suggested RA1 and RA2 differ in GTPase affinity, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and their conserved N-terminal extensions enhance binding. We created Drosophila canoe mutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function, while mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of regulation of adherens junction:cytoskeletal linkage.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

HIV-1 N-myristoylation-dependent hijacking of late endosomes/lysosomes to drive Gag assembly in macrophages. HIV-1 N-肉豆蔻酰化依赖性劫持晚期内体/溶酶体，以驱动巨噬细胞中 Gag 的组装。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-23 DOI: 10.1242/jcs.263588

Gabriel I Guajardo-Contreras, Ana L Abdalla Dos-Santos, Alex Chen, Meijuan Niu, Erwan Beauchamp, Luc G Berthiaume, Alan W Cochane, Andrew J Mouland

{"title":"HIV-1 N-myristoylation-dependent hijacking of late endosomes/lysosomes to drive Gag assembly in macrophages.","authors":"Gabriel I Guajardo-Contreras, Ana L Abdalla Dos-Santos, Alex Chen, Meijuan Niu, Erwan Beauchamp, Luc G Berthiaume, Alan W Cochane, Andrew J Mouland","doi":"10.1242/jcs.263588","DOIUrl":"https://doi.org/10.1242/jcs.263588","url":null,"abstract":"Macrophages represent an important viral reservoir in HIV-1-infected individuals. Different from T cells, HIV-1 assembly in macrophages occurs at intracellular compartments termed virus-containing compartments (VCCs). Our previous research in HeLa cells - in which assembly resembles that found in infected T cells - suggested that late endosomes/lysosomes (LEL) play a role in HIV-1 trafficking towards its assembly sites. However, LEL's role during assembly at VCCs is not fully understood. Herein, we used the HIV-1-inducible cell line THP-1 GagZip as a model to study HIV-1 Gag intracellular trafficking and assembly in macrophages. We demonstrated LEL involvement at VCCs using various microscopy techniques and biochemical approaches. Live-cell imaging revealed that HIV-1 repositions LEL towards the plasma membrane and modulates their motility. We showed that Arl8bmediated LEL repositioning is not responsible of Gag trafficking to VCCs. Additionally, myristoylation inhibition by PCLX-001 decreased Gag presence on endosomes and inhibited VCCs formation, in both cell-line- and primary macrophages. In conclusion, we presented evidence supporting the idea that HIV-1 manipulates the LEL trajectory to guide Gag to VCCs in an N-myristoylation-dependent manner.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

UVB radiation suppresses Dicer expression through β-catenin. 紫外线辐射通过β-catenin抑制Dicer的表达。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-10-23 DOI: 10.1242/jcs.261978

Zackie Aktary, Valérie Petit, Irina Berlin, Jeremy Raymond, Frederique Berger, Nisamanee Charoenchon, Evelyne Sage, Juliette Bertrand, Lionel Larue

引用次数: 0