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Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-20 DOI: 10.1242/jcs.263965
Rachel Bear, Steven A Sloan, Tamara Caspary
{"title":"Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling.","authors":"Rachel Bear, Steven A Sloan, Tamara Caspary","doi":"10.1242/jcs.263965","DOIUrl":"10.1242/jcs.263965","url":null,"abstract":"<p><p>Primary cilia function as specialized signaling centers that regulate many cellular processes including neuron and glia development. Astrocytes possess cilia, but the function of cilia in astrocyte development remains largely unexplored. Critically, dysfunction of either astrocytes or cilia contributes to molecular changes observed in neurodevelopmental disorders. Here, we show that a sub-population of developing astrocytes in the prefrontal cortex are ciliated. This population corresponds to proliferating astrocytes and largely expresses the ciliary protein ARL13B. Genetic ablation of astrocyte cilia in vivo at two distinct stages of astrocyte development results in changes to Sonic Hedgehog (Shh) transcriptional targets. We show that Shh activity is decreased in immature and mature astrocytes upon loss of cilia. Furthermore, loss of cilia in immature astrocytes results in decreased astrocyte proliferation and loss of cilia in mature astrocytes causes enlarged astrocyte morphology. Together, these results indicate that astrocytes require cilia for Shh signaling throughout development and uncover functions for astrocyte cilia in regulating astrocyte proliferation and maturation. This expands our fundamental knowledge of astrocyte development and cilia function to advance our understanding of neurodevelopmental disorders.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663530","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
Definition of the human mitochondrial TOM interactome reveals TRABD as new interacting protein.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-19 DOI: 10.1242/jcs.263576
Metin Özdemir, Silke Oeljeklaus, Schendzielorz Alexander, Marcel Morgenstern, Anusha Valpadashi, Roya Yousefi, Bettina Warscheid, Sven Dennerlein
{"title":"Definition of the human mitochondrial TOM interactome reveals TRABD as new interacting protein.","authors":"Metin Özdemir, Silke Oeljeklaus, Schendzielorz Alexander, Marcel Morgenstern, Anusha Valpadashi, Roya Yousefi, Bettina Warscheid, Sven Dennerlein","doi":"10.1242/jcs.263576","DOIUrl":"https://doi.org/10.1242/jcs.263576","url":null,"abstract":"<p><p>The mitochondrial proteome arises from dual genetic origin. Nuclear-encoded proteins need to be transported across or inserted into two distinguished membranes, and the TOM complex represents the main translocase in the outer mitochondrial membrane. Its composition and regulations have been extensively investigated within yeast cells. However, we have little knowledge of the TOM complex composition within human cells. Here, we have defined the TOM interactome in a comprehensive manner using biochemical approaches to isolate the TOM complex in combination with quantitative mass spectrometry analyses. Within these studies, we defined the pleiotropic nature of the human TOM complex, including new interactors, such as TRABD. Our studies provide a framework to understand the various biogenesis pathways that merge at the TOM complex within human cells.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656951","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 Mia40 substrate Mix17 exposes its N-terminus to the cytosolic side of the mitochondrial outer membrane.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-17 DOI: 10.1242/jcs.263661
Moritz Resch, Johanna S Frickel, Korbinian Dischinger, Rachel Choo Shen Wen, Kai Hell, Max E Harner
{"title":"The Mia40 substrate Mix17 exposes its N-terminus to the cytosolic side of the mitochondrial outer membrane.","authors":"Moritz Resch, Johanna S Frickel, Korbinian Dischinger, Rachel Choo Shen Wen, Kai Hell, Max E Harner","doi":"10.1242/jcs.263661","DOIUrl":"https://doi.org/10.1242/jcs.263661","url":null,"abstract":"<p><p>Mitochondrial architecture and the contacts between the outer and the inner mitochondrial membrane depend on the mitochondrial contact site and cristae organizing system (MICOS) that is highly conserved from yeast to human. Mutations in the mammalian MICOS subunit Mic14/CHCHD10 have been linked to amyotrophic lateral sclerosis and frontotemporal dementia, indicating the importance of this protein. Mic14/CHCHD10 has a yeast ortholog, Mix17, a protein of unknown function, which has not been shown to interact with MICOS so far. As a first step to elucidate the function of Mix17 and its orthologs, we analyzed its interactions, biogenesis and mitochondrial sublocation. We report that Mix17 is no stable MICOS subunit in yeast. Our data suggest that Mix17 is the first Mia40 substrate in the mitochondrial outer membrane. Unlike all other Mia40 substrates, Mix17 spans the outer membrane and exposes its N-terminus to the cytosol. The insertion of Mix17 is likely to be mediated by its interaction with Tom40, the pore of the TOM complex. Moreover, we show that the exposure of Mix17 to the cytosolic side of the membrane depends on its N-terminus.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648589","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
Exploiting the SunTag system to study the developmental regulation of mRNA translation.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-27 DOI: 10.1242/jcs.263457
Alastair Pizzey, Catherine Sutcliffe, Jennifer C Love, Emmanuel Akabuogu, Magnus Rattray, Mark P Ashe, Hilary L Ashe
{"title":"Exploiting the SunTag system to study the developmental regulation of mRNA translation.","authors":"Alastair Pizzey, Catherine Sutcliffe, Jennifer C Love, Emmanuel Akabuogu, Magnus Rattray, Mark P Ashe, Hilary L Ashe","doi":"10.1242/jcs.263457","DOIUrl":"10.1242/jcs.263457","url":null,"abstract":"<p><p>The ability to quantitatively study mRNA translation using SunTag imaging is transforming our understanding of the translation process. Here, we expand the SunTag method to study new aspects of translation regulation in Drosophila. Repression of the maternal hunchback (hb) mRNA in the posterior of the Drosophila embryo is a textbook example of translational control. Using SunTag imaging to quantify translation of maternal SunTag-hb mRNAs, we show that repression in the posterior is leaky, as ∼5% of SunTag-hb mRNAs are translated. In the anterior of the embryo, the maternal and zygotic SunTag-hb mRNAs show similar translation efficiency despite having different untranslated regions (UTRs). We demonstrate that the SunTag-hb mRNA can be used as a reporter to study ribosome pausing at single-mRNA resolution, by exploiting the conserved xbp1 mRNA and A60 pausing sequences. Finally, we adapt the detector component of the SunTag system to visualise and quantify translation of the short gastrulation (sog) mRNA, encoding an essential secreted extracellular BMP regulator, at the endoplasmic reticulum in fixed and live embryos. Together, these tools will facilitate the future dissection of translation regulatory mechanisms during development.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482950","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
Direct neutrophil and T cell contact with macrophages induces release of phagosomally processed PAMPs via eructophagy.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-26 DOI: 10.1242/jcs.263731
Jenny A Nguyen, Tanis L Orsetti, Philip Vernon, Catherine J Greene, Neil McKenna, Robin M Yates
{"title":"Direct neutrophil and T cell contact with macrophages induces release of phagosomally processed PAMPs via eructophagy.","authors":"Jenny A Nguyen, Tanis L Orsetti, Philip Vernon, Catherine J Greene, Neil McKenna, Robin M Yates","doi":"10.1242/jcs.263731","DOIUrl":"10.1242/jcs.263731","url":null,"abstract":"<p><p>Macrophages play a pivotal role in clearing debris and microbes from the microenvironment via phagocytosis and orchestrating local inflammation. Although pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) are understood to mostly be released through the synthesis and secretion of soluble mediators, such as cytokines and eicosanoids, it has been recently proposed that macrophages can release previously phagocytosed and processed PAMPs and DAMPs into the local microenvironment via a process termed eructophagy, and that these, in turn, can activate recently recruited leukocytes. Additionally, it has been commonly observed that local macrophages physically interact with other leukocytes, such as neutrophils and T cells, recruited to sites of inflammation. This study demonstrates that eructophagy in macrophages is significantly induced during physical interaction with neutrophils and T cells, which is mediated by ICAM1 on macrophages and lymphocyte function-associated antigen 1 (LFA1) on neutrophils and T cells. Notably, ICAM1 activation alone is sufficient to trigger eructophagy in macrophages and is dependent on Lyn kinase. Through this mechanism, it is proposed that neutrophils and lymphocytes can influence their own activation by interacting with local macrophages containing PAMP-containing phagolysosomes, which subsequently triggers PAMP release into the local microenvironment through eructophagy.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523606","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
Fibronectin matrix assembly at a glance.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-25 DOI: 10.1242/jcs.263834
Yu Sun, Aaron J Hamlin, Jean E Schwarzbauer
{"title":"Fibronectin matrix assembly at a glance.","authors":"Yu Sun, Aaron J Hamlin, Jean E Schwarzbauer","doi":"10.1242/jcs.263834","DOIUrl":"https://doi.org/10.1242/jcs.263834","url":null,"abstract":"<p><p>The organization and mechanics of extracellular matrix (ECM) protein polymers determine tissue structure and function. Secreted ECM components are assembled into polymers via a cell-mediated process. The specific mechanisms that cells use for assembly are crucial for generating tissue-appropriate matrices. Fibronectin (FN) is a ubiquitous and abundant ECM protein that is assembled into a fibrillar matrix by a receptor-mediated process, and the FN matrix provides a foundation for incorporation of many other proteins into the ECM. In this Cell Science at a Glance article and the accompanying poster, we describe the domain organization of FN and the events that initiate and propagate a stable insoluble network of FN fibrils. We also discuss intracellular pathways that regulate FN assembly and the impact of changes in assembly on disease progression.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700457","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
An ER-associated structure sequesters misassembled FG-rich nucleoporins to help maintain nuclear pore complex function.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-25 DOI: 10.1242/jcs.263659
Madison Pletan, Emily Wang, Luke Gohmann, Billy Tsai
{"title":"An ER-associated structure sequesters misassembled FG-rich nucleoporins to help maintain nuclear pore complex function.","authors":"Madison Pletan, Emily Wang, Luke Gohmann, Billy Tsai","doi":"10.1242/jcs.263659","DOIUrl":"10.1242/jcs.263659","url":null,"abstract":"<p><p>Misassembly of nucleoporins (Nups), central components of the nuclear pore complex (NPC), leads to Nup mislocalization outside of the nuclear envelope. Here we elucidate the fate of mislocalized Nups. To impair Nup assembly, we depleted the structural component Nup98 and found that nucleo-cytoplasmic transport by NPCs remains largely intact. Under this condition, several phenylalanine-glycine-rich Nups (FG-Nups) no longer assemble at the nuclear envelope but instead accumulate at discrete puncta in the endoplasmic reticulum (ER), which we term ER foci. Formation of the foci harboring the misassembled FG-Nups requires the ER morphogenic proteins RTN3, ATL3, and LNP (also known as LNPK). Preventing accumulation of misassembled FG-Nups at the ER foci impairs NPC nucleo-cytoplasmic transport, likely by allowing the misassembled FG-Nups to reach the nuclear envelope, where they disrupt NPC function. Formation of the ER foci is dependent on the kinesin-1 motor. Our results suggest that the ER can sequester misassembled Nups to help maintain NPC function. Because Nup mislocalization is found in many age-related neurodegenerative diseases, our data should illuminate the molecular basis of these pathologic conditions.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624879","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
Science under siege: protecting scientific progress in turbulent times.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-13 DOI: 10.1242/jcs.263970
James Briscoe, Craig E Franklin, Daniel A Gorelick, E Elizabeth Patton, Michael Way
{"title":"Science under siege: protecting scientific progress in turbulent times.","authors":"James Briscoe, Craig E Franklin, Daniel A Gorelick, E Elizabeth Patton, Michael Way","doi":"10.1242/jcs.263970","DOIUrl":"https://doi.org/10.1242/jcs.263970","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624885","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
Co-transcriptional splicing is delayed in the highly expressed thyroglobulin gene.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-19 DOI: 10.1242/jcs.263872
Simon Ullrich, Iliya Nadelson, Stefan Krebs, Helmut Blum, Heinrich Leonhardt, Irina Solovei
{"title":"Co-transcriptional splicing is delayed in the highly expressed thyroglobulin gene.","authors":"Simon Ullrich, Iliya Nadelson, Stefan Krebs, Helmut Blum, Heinrich Leonhardt, Irina Solovei","doi":"10.1242/jcs.263872","DOIUrl":"10.1242/jcs.263872","url":null,"abstract":"<p><p>Transcription of the majority of eukaryotic genes is accompanied by splicing. The timing of splicing varies significantly between introns, transcripts, genes and species. Although quick co-transcriptional intron removal has been demonstrated for many mammalian genes, most splicing events do not occur immediately after intron synthesis. In this study, we utilized the highly expressed Tg gene, which forms exceptionally long transcription loops, providing a convenient model for studying splicing dynamics using advanced light microscopy. Using single-cell oligopainting, we observed a splicing delay occurring several tens of kilobases downstream of a transcribed intron, a finding supported by standard cell population analyses. We speculate that this phenomenon is due to the abnormally high transcriptional rate of the Tg gene, which might lead to a localized deficiency in splicing factors and, consequently, delayed spliceosome assembly on thousands of nascent transcripts decorating the gene. Additionally, we found that, in contrast to what is seen for short introns (<10 kb), the long Tg intron (>50 kb) is spliced promptly, providing further support for the idea that intron length might modulate splicing speed.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656955","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
Macromolecular and cytological changes in fission yeast G0 nuclei.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-27 DOI: 10.1242/jcs.263654
Zhi Yang Tan, Shujun Cai 蔡舒君, Saayli A Paithankar, Tingsheng Liu, Xin Nie, Jian Shi, Lu Gan 甘露
{"title":"Macromolecular and cytological changes in fission yeast G0 nuclei.","authors":"Zhi Yang Tan, Shujun Cai 蔡舒君, Saayli A Paithankar, Tingsheng Liu, Xin Nie, Jian Shi, Lu Gan 甘露","doi":"10.1242/jcs.263654","DOIUrl":"10.1242/jcs.263654","url":null,"abstract":"<p><p>When starved of nitrogen, cells of the fission yeast Schizosaccharomyces pombe enter a quiescent 'G0' state with smaller nuclei and transcriptional repression. The genomics of S. pombe G0 cells has been well studied, but much of its nuclear cell biology remains unknown. Here, we use confocal microscopy, immunoblots and electron cryotomography to investigate the cytological, biochemical and ultrastructural differences between S. pombe proliferating, G1-arrested and G0 cell nuclei, with an emphasis on the histone acetylation, RNA polymerase II fates and macromolecular complex packing. Compared to proliferating cells, G0 cells have lower levels of histone acetylation, nuclear RNA polymerase II and active transcription. The G0 nucleus has similar macromolecular crowding yet fewer chromatin-associated multi-megadalton globular complexes. Induced histone hyperacetylation during nitrogen starvation results in cells that have larger nuclei and therefore chromatin that is less compact. However, these histone-hyperacetylated cells remain transcriptionally repressed with similar nuclear crowding. Canonical nucleosomes - those that resemble the crystal structure - are rare in proliferating, G1-arrested and G0 cells. Our study therefore shows that extreme changes in nucleus physiology are possible without extreme reorganization at the macromolecular level.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515822","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
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