Connor Ross, Paula A Balestrini, Lawrence E Bates, Takuya Azami, Taiye Adakole, Maxine Semple, Marika Salonna, Richard Gyuris, Jennifer Nichols, Norah E Fogarty, Stefan Hoppler
{"title":"WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm.","authors":"Connor Ross, Paula A Balestrini, Lawrence E Bates, Takuya Azami, Taiye Adakole, Maxine Semple, Marika Salonna, Richard Gyuris, Jennifer Nichols, Norah E Fogarty, Stefan Hoppler","doi":"10.1242/jcs.264257","DOIUrl":"10.1242/jcs.264257","url":null,"abstract":"<p><p>Embryonic stem (ES) cell research has uncovered different requirements for WNT/β-catenin signalling in human naïve pluripotent cells compared to the mouse paradigm. It is therefore important to study WNT/β-catenin signalling directly in models that recapitulate early human development. Since TCF/LEF transcription factors mediate regulation of target genes downstream of WNT/β-catenin signalling, we examined the regulation, expression and protein localisation of the four TCF/LEF genes by analysing in vitro 'snapshots' of human development, leveraging naïve and primed pluripotent cells, blastoids and preimplantation blastocysts. Strikingly, we comprehensively confirm clear differences between mouse and human pluripotent stem cells, suggesting their differential requirements for WNT signalling reflects a pluripotent state-dependent manner. Human naïve ES cells express considerably lower levels of TCF7L1, unlike their mouse counterparts. TCF7L2 is robustly expressed in the trophectoderm derived from naïve ES cells, in blastoids and human preimplantation blastocysts. In primed pluripotent stem cells, active WNT/β-catenin signalling induces the expression of both TCF7 and LEF1, concomitant with hallmark gastrulation markers. The expression of human TCF/LEF genes indicates a differential requirement for WNT/β-catenin signalling throughout early human embryo development that warrants further investigation.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955575","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}
Bethany F Campbell, Dhanya Kalathil, Uma J Patel, Ashlei R Williams, Maitreyi E Das
{"title":"Endocytic patch dynamics are differentially regulated at distinct cell sites in fission yeast.","authors":"Bethany F Campbell, Dhanya Kalathil, Uma J Patel, Ashlei R Williams, Maitreyi E Das","doi":"10.1242/jcs.263873","DOIUrl":"10.1242/jcs.263873","url":null,"abstract":"<p><p>Endocytosis promotes polarity and growth in eukaryotes. In Schizosaccharomyces pombe fission yeast, endocytosis occurs at the polarized cell ends and division site and at the non-polarized cell sides. Our characterization of endocytic actin patches shows that they are differentially regulated. The patches at the cell ends and division site internalize successfully, whereas those at the sides are weak and erratic. The major regulator of cell polarity, Cdc42, and its target Pak1 kinase (also known as Shk1 and Orb2) only localize to the cell ends and division site. We find that these proteins regulate assembly and internalization of patches at these sites but not at the cell sides. Moreover, Cdc42 specifically activated by the guanine-nucleotide-exchange factor (GEF) Gef1 promotes proper patch dynamics. Endocytosis requires phosphorylation of the type I myosin Myo1 by the Pak1 kinase. Myo1 localizes to the cell ends, division site and the cell sides. We find that unlike Cdc42 and Pak1, Myo1 also promotes patch assembly at the cell sides. Our data indicate that although Myo1 can globally promote branched actin assembly, successful endocytic patch dynamics and internalization at polarized sites require Cdc42 and Pak1 kinase.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955369","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}
Tiago J Dantas, Diogo M Abreu, Maria J G De-Castro, Ana R G De-Castro, Noopur V Khobrekar, Sónia A Rocha, Carla M C Abreu
{"title":"Dynein-2 requires HSP90 chaperone activity to ensure robust retrograde IFT and ciliogenesis.","authors":"Tiago J Dantas, Diogo M Abreu, Maria J G De-Castro, Ana R G De-Castro, Noopur V Khobrekar, Sónia A Rocha, Carla M C Abreu","doi":"10.1242/jcs.264034","DOIUrl":"https://doi.org/10.1242/jcs.264034","url":null,"abstract":"<p><p>The microtubule motor dynein-2 is responsible for retrograde intraflagellar transport (IFT), a process critical for cilia assembly and cilium-dependent signaling. Mutations in genes encoding dynein-2 subunits interfere with ciliogenesis and are among the most frequent causes of skeletal ciliopathies. Despite its importance, little is known regarding dynein-2 assembly and regulation. Here, we identify the molecular HSP90 chaperone as a critical regulator of dynein-2 complex stability and function. Pharmacological inhibition of HSP90 causes a severe decrease in the levels of dynein-2 subunits, without detectable alterations in cytoplasmic dynein-1 and the anterograde IFT kinesin-2 motor KIF3A. Consistent with disrupted dynein-2 function, HSP90 inhibition progressively disrupts retrograde IFT and severely impairs ciliogenesis. We demonstrate that HSP90 associates with the dynein-2 complex, promoting its assembly and stabilization. These results establish dynein-2 as a novel HSP90 client and provide important mechanistic insights into the regulation of dynein-2 assembly.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033451","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}
Alyssa B Long, Isabella M Wilson, Tiffany T Terry, Robert E Van Sciver, Tamara Caspary
{"title":"ARL13B-Cerulean rescues Arl13b-null mouse from embryonic lethality and reveals a role for ARL13B in spermatogenesis.","authors":"Alyssa B Long, Isabella M Wilson, Tiffany T Terry, Robert E Van Sciver, Tamara Caspary","doi":"10.1242/jcs.264009","DOIUrl":"10.1242/jcs.264009","url":null,"abstract":"<p><p>ARL13B is a regulatory GTPase enriched in cilia, making it a popular marker for this organelle. Arl13bhnn/hnn mice lack ARL13B expression, die during midgestation, and exhibit defects in ciliogenesis. The R26Arl13b-Fucci2aR biosensor mouse line directs the expression of fluorescently tagged full-length Arl13b cDNA upon Cre recombination. To determine whether constitutive, ubiquitous expression of ARL13B-Cerulean can replace endogenous gene expression, we generated Arl13bhnn/hnn animals expressing ARL13B-Cerulean. We show that Arl13bhnn/hnn;Arl13b-Cerulean mice survive to adulthood with no obvious physical or behavioral defects, indicating that the fluorescently tagged protein can functionally replace the endogenous protein during development. However, we observed that rescued males failed to sire offspring, revealing a role for ARL13B in spermatogenesis. This work shows that the R26Arl13b- Fucci2aR mouse contains an inducible allele of Arl13b capable of functioning in most tissues and biological processes.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015481","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}
Yubo Zou, Nicolas Allen, Emaan Rauf, Deborah Leckband
{"title":"Epidermal growth factor receptor is an essential component in E-cadherin force-transduction complexes.","authors":"Yubo Zou, Nicolas Allen, Emaan Rauf, Deborah Leckband","doi":"10.1242/jcs.264350","DOIUrl":"https://doi.org/10.1242/jcs.264350","url":null,"abstract":"<p><p>We present evidence that the association of Epithelial (E)-cadherin (CHD1) extracellular domain and epidermal growth factor receptor (EGFR, ErbB1) is obligatory for cadherin force transduction signaling. E-cadherin and EGFR associate at cell surfaces, independent of their cytoplasmic domains, and tension on E-cadherin activates EGFR signaling. Using engineered cadherin mutants that disrupt co-immunoprecipitation with EGFR, but not adhesion, we show that the hetero-receptor complex is required to mechanically activate signaling and downstream cytoskeletal remodeling at cadherin adhesions. The mutants localized the essential region on E-cadherin to the extracellular region and domain 4, EC4. The ectodomain is also required for hetero-receptor co-localization at intercellular junctions. Although the E-cadherin mutants disrupt EGFR signaling, integrin pre-activation together with tension rescues cytoskeletal reinforcement at cadherin adhesions, confirming the role of integrins in intercellular force transduction. Furthermore, although E-cadherin suppresses EGFR-mediated proliferation, in response to extracellular matrix stiffening, the force-sensitive hetero-receptor complex regulates growth factor-dependent epithelial proliferation. These findings support the hypothesis that E-cadherin complexes with EGFR are mechano-switches at cell-cell contacts that directly couple intercellular force fluctuations to mitogen-dependent signaling.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000678","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}
Collin M Ainslie, Krishna Patel, Yen T B Tran, Samuel C Bartley, Navaneetha Krishnan Bharathan, Volker Spindler, Alexa L Mattheyses
{"title":"The desmoplakin tail domain position in the desmosomal plaque is isoform dependent.","authors":"Collin M Ainslie, Krishna Patel, Yen T B Tran, Samuel C Bartley, Navaneetha Krishnan Bharathan, Volker Spindler, Alexa L Mattheyses","doi":"10.1242/jcs.263906","DOIUrl":"10.1242/jcs.263906","url":null,"abstract":"<p><p>Desmoplakin (DP, also known as DSP) is a key protein in desmosomes, cell-cell junctions that provide mechanical integrity to the skin and heart. DP has three isoforms, DPI, DPIa and DPII, which differ only in the length of their central rod domain and arise from alternative splicing. Alterations of tissue-specific DP isoform expression underlie rare skin and heart diseases. Desmosomes are macromolecular complexes, and their protein architecture is essential for physiological function. Here, we used direct stochastic optical reconstruction microscopy (dSTORM) to define the architectural arrangement of DPI, DPIa and DPII with a C-terminal mEGFP expressed in DP-knockout (KO) HaCaT cells. We show the DP tail domain position is isoform dependent and correlates with rod length. DPI has the longest rod domain, and its tail is farthest from the plasma membrane, whereas DPII has the shortest rod and is closest. This variable tail location architecture was conserved in wild-type HaCaT cells expressing both DPI and DPII. We propose a novel aligned angle model, with each DP isoform co-aligned at an acute angle relative to the plasma membrane. These results provide insight into how DP architecture supports desmosome function.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816750","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}
Guglielmo Rambaldelli, Valeria Manara, Andrea Vutera Cuda, Giovanni Bertalot, Marianna Penzo, Paola Bellosta
{"title":"Drosophila and human cell studies reveal a conserved role for CEBPZ, NOC2L and NOC3L in rRNA processing and tumorigenesis.","authors":"Guglielmo Rambaldelli, Valeria Manara, Andrea Vutera Cuda, Giovanni Bertalot, Marianna Penzo, Paola Bellosta","doi":"10.1242/jcs.264096","DOIUrl":"10.1242/jcs.264096","url":null,"abstract":"<p><p>NOC1, NOC2 and NOC3 are evolutionarily conserved nucleolar proteins that play an essential role in the maturation and processing of ribosomal RNA (rRNA). NOC1 in Drosophila is necessary to sustain rRNA processing, whereas its depletion leads to impaired polysome formation, reduced protein synthesis and induces apoptosis. In this study, we demonstrated that the RNA-regulatory functions of NOC1 are conserved in vertebrates, where the reduction of CEBPZ, the homolog of NOC1, leads to the accumulation of unprocessed 45S pre-rRNA, a reduction in protein synthesis, and inhibition of cell growth. Gene Ontology and bioinformatic analyses of CEBPZ, NOC2L and NOC3L in tumors highlight a significant correlation between their expression and processes that regulate rRNA processing and ribosomal maturation. Moreover, comparative analysis of TCGA datasets from tumor databases revealed that CEBPZ, NOC2L and NOC3L exhibit contrasting expression patterns across tumor types. This context-dependent behavior suggests that overexpression of these proteins might promote tumor growth, whereas reduced expression could exert tumor-suppressive effects, underscoring their complex and unexpected regulatory roles in cancer.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873372","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}
{"title":"Revisiting secretory granule fusion at vesicular pseudopodia.","authors":"Nadav Scher, Ori Avinoam","doi":"10.1242/jcs.263980","DOIUrl":"10.1242/jcs.263980","url":null,"abstract":"<p><p>Secretory granules are specialized vesicles that package large amounts of cargo, such as hormones, enzymes and mucous. They are typically stored intracellularly until an extracellular signal initiates exocytosis, characterized by fusion between the secretory vesicles and the plasma membrane, resulting in cargo release to the environment. Observations made in the 1970s suggested that some secretory granules project a pseudopodium from their surface where fusion with the cell surface occurs. However, these observations fell into obscurity, leaving the mechanistic and physiological significance of vesicular pseudopodia unknown. This knowledge gap prompted us to consolidate the current knowledge on pseudopodia and exocytosis, which has led us to the hypothesis that pseudopodia are an evolutionarily conserved adaptation of large secretory granules important for efficient fusion and cargo release. In this Perspective, we aim to reignite interest in elucidating the mechanisms governing pseudopodia structure and function in the context of the unique challenges faced by secretory tissues utilizing large secretory granules.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 17","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955606","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}
{"title":"'First Persons' through the decades - 100 years of notable scientists in Journal of Cell Science.","authors":"Amelia Glazier","doi":"10.1242/jcs.264351","DOIUrl":"https://doi.org/10.1242/jcs.264351","url":null,"abstract":"<p><p>In 2017, Journal of Cell Science (JCS) began inviting the first authors of published research articles to share a bit about themselves and their work through our 'First Person' short interview series, with the aim of helping early-career researchers (ECRs) promote their exciting science and advance their careers. Over the last 7 years, we have now published over 700 'First Person' interviews from ECRs around the world. But JCS has been around much longer than that - in fact, JCS was first established in 1853 as the Quarterly Journal of Microscopical Science (QJMS), re-branded as JCS in 1966. In celebration of the 100th anniversary year of our publisher, The Company of Biologists, we've decided to introduce our readers to some notable scientists who published their own first-author papers in QJMS or JCS over the last century. Below, you can learn about the remarkable careers of ten distinguished researchers, one from each decade from the 1920s to the 2010s, who have made significant contributions to the cell biology community. As we consider our next 100 years, we look forward to supporting the scientific careers of many more 'First Persons' to come.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 17","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033509","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}
{"title":"The Company of Biologists and the British Society for Cell Biology: a long-standing relationship.","authors":"Saanjbati Adhikari","doi":"10.1242/jcs.264366","DOIUrl":"10.1242/jcs.264366","url":null,"abstract":"<p><p>The British Society for Cell Biology (BSCB), established in 1965, is a charitable organisation that 'aims to promote research and exchange of information relating to all branches of cell biology'. The Society hosts and supports meetings and conferences relevant to cell biology and plays a crucial role in raising awareness towards scientific policies in the UK and Ireland. Since its early days, the society has held strong ties with The Company of Biologists, a not-for-profit publisher that strives to inspire biology and support biologists. In this Essay, to commemorate the 100-year anniversary of The Company of Biologists, I discuss the evolution of the BSCB and highlight its relationship with the Company from when the Society was founded through to the present day.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 17","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064748","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}