Journal of cell science最新文献_第9页

Evaluating the roles of ion channels in cellular force sensing. 评估离子通道在细胞力感应中的作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 DOI: 10.1242/jcs.264038

Samantha Webster, Remi Brynn, Kate Poole

{"title":"Evaluating the roles of ion channels in cellular force sensing.","authors":"Samantha Webster, Remi Brynn, Kate Poole","doi":"10.1242/jcs.264038","DOIUrl":"https://doi.org/10.1242/jcs.264038","url":null,"abstract":"Mechanosensitive ion channels are found across all classes of life, suggesting that cellular force sensing is an ancient sense. In mammals, mechanosensitive ion channels are expressed in many cells and tissues, and disrupting their function can impact an array of physiological processes. The identification and characterisation of mammalian mechanosensitive ion channels has been driven by in vitro patch-clamp electrophysiology studies. However, challenges arise when applying insights from these biophysical measurements across scales. Electrophysiology studies do not capture the complexity of force sensing in vivo, where the nature of mechanical loading, the mechanics of the local environment and the co-expression of accessory molecules can all influence mechanosensitive ion channel function. In addition, a nuanced perspective acknowledging the varying roles that ion channels can play in force-sensing pathways and the distinctions in activation profiles of mechanosensitive ion channels is required to better understand channel-mediated mechanotransduction. In this Opinion article, by synthesising our knowledge of these activation profiles gleaned from in vitro studies, we argue that only by considering mechanosensitive ion channel function within an appropriate cellular and mechanical context will we be able to better understand the roles of this fascinating class of molecule in mammalian cells in vivo.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 15","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760203","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

TMEM184B modulates endolysosomal acidification via the vesicular proton pump. 跨膜蛋白184B （TMEM184B）通过囊泡质子泵调节内溶酶体酸化。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-08 DOI: 10.1242/jcs.263908

Elizabeth B Wright, Erik G Larsen, Marco Padilla-Rodriguez, Paul R Langlais, Martha R C Bhattacharya

{"title":"TMEM184B modulates endolysosomal acidification via the vesicular proton pump.","authors":"Elizabeth B Wright, Erik G Larsen, Marco Padilla-Rodriguez, Paul R Langlais, Martha R C Bhattacharya","doi":"10.1242/jcs.263908","DOIUrl":"10.1242/jcs.263908","url":null,"abstract":"Disruption of endolysosomal acidification causes toxic protein accumulation and neuronal dysfunction linked to neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms regulating neuronal endolysosomal pH remain unclear. Transmembrane protein 184B (TMEM184B) is a conserved seven-pass transmembrane protein that is essential for synaptic function, and its sequence disruption is associated with neurodevelopmental disorders. Here, we identify TMEM184B as a key regulator of endolysosomal acidification. TMEM184B localizes to early and late endosomes, and proteomic analysis confirms that TMEM184B interacts with endosomal proteins, including the vacuolar ATPase (V-ATPase), a multi-subunit proton pump crucial for lumenal acidification. Tmem184b-mutant mouse cortical neurons have reduced endolysosomal acidification compared to wild-type neurons. We find reductions in V-ATPase complex assembly in Tmem184b-mutant mouse brains, suggesting that TMEM184B facilitates endosomal flux by promoting V-ATPase activity. These findings establish TMEM184B as a regulator of neuronal endolysosomal acidification and provide mechanistic insight into its role in TMEM184B-associated nervous system disorders.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Transcriptional adaptation after deletion of Cdc42 in primary T cells. 原代T细胞中Cdc42缺失后的转录适应。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-04 DOI: 10.1242/jcs.263826

Adam M Rochussen, Claire Y Ma, Gillian M Griffiths

{"title":"Transcriptional adaptation after deletion of Cdc42 in primary T cells.","authors":"Adam M Rochussen, Claire Y Ma, Gillian M Griffiths","doi":"10.1242/jcs.263826","DOIUrl":"10.1242/jcs.263826","url":null,"abstract":"Cdc42 is a Rho family GTPase known for its central role in cell polarity and cytoskeletal regulation. To understand the role of Cdc42 in polarised secretion from cytotoxic T lymphocytes (CTLs) we used CRISPR/Cas9 gene deletion. Although Cdc42-deleted CTLs initially showed reduced cytotoxicity for up to 2 days after CRISPR-mediated deletion, full secretion and cytotoxicity was rapidly restored and even enhanced while CDC42 protein remained absent. In contrast, chemical inhibition of CDC42 using CASIN consistently decreased secretion in wild-type cells, but had no impact on Cdc42-deleted CTLs, confirming the specificity of this inhibitor. Comparative proteomics and transcriptomics of CTLs after Cdc42 deletion revealed transcriptional changes that could support improved T cell function, including compensation via other Rho GTPases. Targeting the promoter region of Cdc42 did not trigger transcriptional adaptation, consistent with a nonsense-mediated decay mechanism of genetic compensation. Our work highlights the importance of taking orthogonal approaches to study protein function and reveals the remarkable robustness of primary T cells to adapt to loss of an essential gene.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Survivin can alter mitochondrial architecture by regulating phosphatidylethanolamine synthesis. Survivin可以通过调节磷脂酰乙醇胺合成来改变线粒体结构。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-04 DOI: 10.1242/jcs.263689

Lucia Dunajová, Amelia Townley, Sophie Rochette, Denise McLean, Jamie R M Webster, Sally P Wheatley

{"title":"Survivin can alter mitochondrial architecture by regulating phosphatidylethanolamine synthesis.","authors":"Lucia Dunajová, Amelia Townley, Sophie Rochette, Denise McLean, Jamie R M Webster, Sally P Wheatley","doi":"10.1242/jcs.263689","DOIUrl":"10.1242/jcs.263689","url":null,"abstract":"Survivin (encoded by BIRC5) is an essential protein with established roles in mitosis and the inhibition of apoptosis. It is overexpressed in cancers, its abundance correlating with resistance to radiotherapies and chemotherapies. Survivin expression is normally limited to G2 and M phases; however, in cancer cells, it is also present during interphase and gains access to the mitochondria. Phosphatidylethanolamine (PE) is a phospholipid that facilitates negative curvature of membranes. It is enriched in the cytokinetic furrow and mitochondria, where it enables tight packing of the cristae and the increased accommodation of proteins. Here, we report the remarkable discovery that mitochondrial survivin regulates phosphatidylserine decarboxylase activity, thereby affecting PE availability. This novel molecular insight suggests that some apparently disparate roles of this 'multitasking' protein might be fundamentally linked to membrane architecture, and offers a new perspective on its contribution to cancer and potentially other metabolic disorders.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 15","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Why would anyone want to be a scientist? 为什么会有人想成为科学家呢？

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 DOI: 10.1242/jcs.264284

Martin A Schwartz

引用次数: 0

Syntaxin-2 balances phagocytic uptake and phagolysosomal clearance in macrophages. Syntaxin-2在巨噬细胞中平衡吞噬摄取和吞噬溶酶体清除。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-06 DOI: 10.1242/jcs.263855

Suman Samanta, Abhrajyoti Nandi, Rupak Datta, Subhankar Dolai

{"title":"Syntaxin-2 balances phagocytic uptake and phagolysosomal clearance in macrophages.","authors":"Suman Samanta, Abhrajyoti Nandi, Rupak Datta, Subhankar Dolai","doi":"10.1242/jcs.263855","DOIUrl":"10.1242/jcs.263855","url":null,"abstract":"Phagocytosis engulfs receptor-bound particles within phagosomes that mature into acidic, hydrolase-enriched phagolysosomes for content degradation. Although an essential process for host defense and homeostasis, defective or uncontrolled phagocytosis can be detrimental. We report here, that syntaxin-2 (Stx2), a poorly characterized SNARE in phagocytes, defines the course of macrophage phagocytosis by coordinating surface receptor density, phagosome biogenesis and maturation. Stx2 is expressed primarily on the plasma membrane, early endosomes and phagosomes. Stx2 knockdown (Stx2-KD) increases entrapment and uptake of IgG-opsonized particles owing to dysregulated formation and expansion of phagocytic cups driven by elevated IgG receptor recycling and trafficking of early endosomes and VAMP4-positive post-Golgi compartments to phagocytic cups. Interestingly, Stx2-KD decreases secretion of pro-cathepsins and increases lysosome content. However, Stx2-KD impedes phagosome maturation by preventing coalescence with late endosomes, lysosomes and reducing phagosomal acidification. Consequently, Stx2-depleted macrophages exhibit aberrant uptake of IgG-opsonized bacteria and impaired digestion, resulting in increased intracellular accumulation of intact bacteria. Collectively, Stx2 critically balances phagocytic uptake and phagolysosomal clearance in macrophages, suggesting that Stx2 could be an attractive target to modulate phagocytosis plasticity and to control aberrant phagocytosis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The adhesion plaque mediates fluid discharge and duplication of the contractile vacuole complex in Trypanosoma cruzi. 在克氏锥虫中，黏附斑块介导液体排出和收缩液泡复合体的复制。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-06 DOI: 10.1242/jcs.263810

Ingrid Augusto, Wendell Girard-Dias, Alejandra Schoijet, Guillermo Daniel Alonso, Veronica Jimenez, Wanderley de Souza, Kildare Miranda

{"title":"The adhesion plaque mediates fluid discharge and duplication of the contractile vacuole complex in Trypanosoma cruzi.","authors":"Ingrid Augusto, Wendell Girard-Dias, Alejandra Schoijet, Guillermo Daniel Alonso, Veronica Jimenez, Wanderley de Souza, Kildare Miranda","doi":"10.1242/jcs.263810","DOIUrl":"10.1242/jcs.263810","url":null,"abstract":"This work explores the intricate process of osmoregulation in Trypanosoma cruzi, the causative agent of Chagas disease, with a specific focus on the mechanisms of fluid discharge by the contractile vacuole complex (CVC) and the role of the adhesion plaque (AP), a structure whose densities are located in the membrane domain shared by the CVC and the flagellar pocket. Cryopreparation of T. cruzi samples, combined with volume electron microscopy techniques, allowed for a comprehensive analysis of the essential mechanisms underlying the structural changes that take place in the AP during osmotic stress. Remodeling of the AP coupled to membrane fusion events leads to the formation of pores that connect the flagellar pocket and the CVC. The fluid discharge process followed sequential steps of pore opening, expansion and closure, to allow membrane fusion. Additionally, this study uncovers structural variations in the CVC during cellular replication, providing insights into the cellular biology and physiology of trypanosomatids.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cell cycle- and dose-dependent effects on mitochondrial DNA copy number variation following irradiation. 细胞周期和剂量依赖性对辐照后线粒体DNA拷贝数变异的影响。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-08 DOI: 10.1242/jcs.263642

Ryosuke Seino, Kai Nishikubo, Hisanori Fukunaga

{"title":"Cell cycle- and dose-dependent effects on mitochondrial DNA copy number variation following irradiation.","authors":"Ryosuke Seino, Kai Nishikubo, Hisanori Fukunaga","doi":"10.1242/jcs.263642","DOIUrl":"10.1242/jcs.263642","url":null,"abstract":"Cell survival after irradiation depends on the cell cycle at the time of exposure. This has been thought to be due to cell cycle-dependent nuclear DNA damage repair mechanisms. Here, we show the relationships between the exposed dose, the cell cycle phase at the time of exposure and changes in mitochondrial DNA copy numbers (mtDNAcn) after irradiation. We used a fluorescent ubiquitylation-based cell cycle indicator (FUCCI), which allows visualization of the cell cycle, and confirmed cell cycle synchronization in human cervical HeLa cells. In synchronous HeLa-FUCCI cells, the mtDNAcn changed with the progression of the cell cycle. Also, G1 phase-synchronized cells showed a dose-dependent increase of mtDNAcn at 48 h after X-ray exposure, whereas G2 cells showed a dose-dependent increase at 24 h. In addition, S phase-synchronized cells showed a dose-dependent increase at 24 and 48 h after irradiation. These results showed the cell cycle- and dose-dependent effects on mtDNAcn after irradiation, which might shed light on the emerging role of mitochondrial genome and in cell survival.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Emerging roles of lipid transfer protein dimerization. 脂质转移蛋白二聚化的新作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-08-01 Epub Date: 2025-08-08 DOI: 10.1242/jcs.263971

Shalom Borst Pauwels, Jacques Neefjes, Birol Cabukusta

{"title":"Emerging roles of lipid transfer protein dimerization.","authors":"Shalom Borst Pauwels, Jacques Neefjes, Birol Cabukusta","doi":"10.1242/jcs.263971","DOIUrl":"10.1242/jcs.263971","url":null,"abstract":"The unique lipid composition of organelles defines their identity and is fundamental to their function. Lipid transfer proteins perform non-vesicular trafficking of lipids among cellular membranes to maintain their lipid compositions. Lipid transfer protein-mediated lipid trafficking is also essential for creating sub-organellar nano-domains that can recruit functional proteins or change the biophysical properties of membranes. The latest research focusing on the homo- and hetero-dimerization of lipid transfer proteins highlights the functional implications and the clinical significance of these events. Dimerization promotes lipid transfer protein localization at membrane contact sites and mediates the assembly of lipid transfer protein super-complexes to synchronize the transfer of different lipid types between organelles. Meanwhile, abnormal lipid flows caused by disarrangements in lipid transfer protein dimerization disturb organelle lipid landscapes, which has clinical consequences. This Review discusses the latest developments regarding the dimerization of lipid transfer proteins and their adaptor proteins that are critical for lipid trafficking between the organelles of the cell.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 15","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

RHOA-dependent regulation of mitochondrial remodeling and cell motility in hypoxia-exposed gastric epithelial cells. 缺氧暴露的胃上皮细胞线粒体重塑和细胞运动的rhoa依赖性调节。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-07-15 Epub Date: 2025-07-30 DOI: 10.1242/jcs.263690

Aranya Pal, Prabin Bawali, Abhisek Brahma, Smruti Ranjan Rana, Rakesh Mohapatra, Debashish Chakraborty, Indrajit Poirah, Supriya Samal, Smaran Banerjee, Duane T Smoot, Hassan Ashktorab, Asima Bhattacharyya

{"title":"RHOA-dependent regulation of mitochondrial remodeling and cell motility in hypoxia-exposed gastric epithelial cells.","authors":"Aranya Pal, Prabin Bawali, Abhisek Brahma, Smruti Ranjan Rana, Rakesh Mohapatra, Debashish Chakraborty, Indrajit Poirah, Supriya Samal, Smaran Banerjee, Duane T Smoot, Hassan Ashktorab, Asima Bhattacharyya","doi":"10.1242/jcs.263690","DOIUrl":"10.1242/jcs.263690","url":null,"abstract":"Mitochondrial appearance distinctively reflects cellular stress. Hypoxia, one of the most fundamental stressors, drives tumor progression, impacting mitochondrial structure and function. RAS homolog family member A (RHOA), a key regulator of cell motility, is frequently upregulated in response to hypoxia across cancers. However, its behavior under hypoxic conditions in gastric cancer (GC) remains largely unexplored. Additionally, to what extent the role of RHOA in cell motility is mediated through an influence on mitochondrial reshaping is elusive. Here, we show that an elevated RHOA level in GC cells triggers mitochondrial shape changes, from tubular to the stress-associated lasso and donut, correlating with increased reactive oxygen species (ROS). However, RHOA-overexpressing cells experiencing hypoxia exhibited increased migration, despite reduced mitochondrial fission and ROS levels. RHO-associated coiled-coil kinase (ROCK) inhibition impaired mitochondrial shape changes, suggesting it has a role in mitochondrial remodeling. These results indicate a unique adaptive response to hypoxia, where RHOA upregulation increases motility and modulates mitochondrial plasticity in GC cells. In summary, RHOA-mediated mitochondrial reshaping might serve as a key regulator in tumor cell adaptation and migration in low-oxygen environments.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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