Journal of cell science最新文献_第10页

An ER-associated structure sequesters misassembled FG-rich nucleoporins to help maintain nuclear pore complex function. 内质网相关结构隔离了错误组装的fg - nps，以帮助维持NPC功能。

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":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050091/pdf/","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":"OA","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. 围攻中的科学：在动荡时期保护科学进步。

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

引用次数: 0

Co-transcriptional splicing is delayed in the highly expressed thyroglobulin gene. 高表达的甲状腺球蛋白基因的共转录剪接延迟。

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":"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.","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. 裂变酵母G0细胞核的大分子和细胞学变化。

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":"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.","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

Cell biology meets climate resilience - a call to action. 细胞生物学与气候适应能力相遇——行动呼吁。

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.263987

Mónica Bettencourt-Dias, Amy Gladfelter, Gautam Dey, Samara L Reck-Peterson

引用次数: 0

The formation of chaperone-rich GET bodies depends on the tetratricopeptide repeat region of Sgt2 and is reversed by NADH. 富含伴侣的GET小体的形成依赖于Sgt2的四肽重复区，并被NADH逆转。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-15 Epub Date: 2025-03-20 DOI: 10.1242/jcs.263616

Jonas Jennrich, Ákos Farkas, Henning Urlaub, Blanche Schwappach, Katherine E Bohnsack

{"title":"The formation of chaperone-rich GET bodies depends on the tetratricopeptide repeat region of Sgt2 and is reversed by NADH.","authors":"Jonas Jennrich, Ákos Farkas, Henning Urlaub, Blanche Schwappach, Katherine E Bohnsack","doi":"10.1242/jcs.263616","DOIUrl":"10.1242/jcs.263616","url":null,"abstract":"The guided-entry of tail-anchored proteins (GET) pathway is a post-translational targeting route to the endoplasmic reticulum (ER). Upon glucose withdrawal, the soluble GET proteins re-localize to dynamic cytosolic foci, here termed GET bodies. Our data reveal that the pre-targeting complex components, Sgt2 and the Get4-Get5 heterodimer, and the Get3 ATPase play important roles in the assembly of these structures in Saccharomyces cerevisiae. More specifically, the TPR region of Sgt2 is required as a GET body scaffold. Systematic compositional analyses of GET bodies reveal their chaperone-rich nature and the presence of numerous proteins involved in metabolic processes. Temporal analyses of GET body assembly demonstrate the sequential recruitment of different chaperones, and we discover the requirement of Sis1 and Sti1 for maintaining the dynamic properties of these structures. In vivo, NADH derived from the oxidation of ethanol to acetaldehyde can induce GET body disassembly in a reaction depending on the alcohol dehydrogenase Adh2 and in vitro, addition of NADH resolves GET bodies. This suggests a mechanistic basis for their formation and disassembly in response to the metabolic shift caused by glucose withdrawal and re-addition.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458138","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

γ-tubulin mediates DNA double-strand break repair. γ-微管蛋白介导DNA双链断裂修复。

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.262255

Abhishikt David Solomon, Odjo G Gouttia, Ling Wang, Songli Zhu, Feifei Wang, Yanqui Li, Mohammadjavad Paydar, Tadayoshi Bessho, Benjamin H Kwok, Aimin Peng

{"title":"γ-tubulin mediates DNA double-strand break repair.","authors":"Abhishikt David Solomon, Odjo G Gouttia, Ling Wang, Songli Zhu, Feifei Wang, Yanqui Li, Mohammadjavad Paydar, Tadayoshi Bessho, Benjamin H Kwok, Aimin Peng","doi":"10.1242/jcs.262255","DOIUrl":"10.1242/jcs.262255","url":null,"abstract":"Double-strand breaks (DSBs) in DNA pose a critical threat to genomic integrity, potentially leading to the onset and progression of various diseases, including cancer. Cellular responses to such lesions entail sophisticated repair mechanisms primarily mediated by non-homologous end joining (NHEJ) and homologous recombination (HR). Interestingly, the efficient recruitment of repair proteins and completion of DSB repair likely involve complex, inter-organelle communication and coordination of cellular components. In this study, we report a role of γ-tubulin in DSB repair. γ-tubulin is a major microtubule nucleation factor governing microtubule dynamics. We show that γ-tubulin is recruited to the site of DNA damage and is required for efficient DSB repair via both NHEJ and HR. Suppression of γ-tubulin impedes DNA repair and exacerbates DNA damage accumulation. Furthermore, γ-tubulin mediates the mobilization and formation of DNA damage foci, which serve as repair centers, thereby facilitating the recruitment of HR and NHEJ repair proteins on damaged chromatin. Finally, pharmacological inhibition of γ-tubulin enhances the cytotoxic effect of DNA-damaging agents, consistent with the DNA repair function of γ-tubulin, and underscoring the potential of its therapeutic intervention in cancer therapy.","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/PMC12050090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709950","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 compression - relevance, mechanotransduction mechanisms and tools. 细胞压缩-相关性，机械转导机制和工具。

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.263704

Laura M Faure, Valeria Venturini, Pere Roca-Cusachs

引用次数: 0

Dynein-driven regulation of postsynaptic membrane architecture and synaptic function. 动力蛋白驱动的突触后膜结构和突触功能的调节。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-12 DOI: 10.1242/jcs.263844

Amanda L Neisch, Thomas Pengo, Adam W Avery, Min-Gang Li, Thomas S Hays

{"title":"Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.","authors":"Amanda L Neisch, Thomas Pengo, Adam W Avery, Min-Gang Li, Thomas S Hays","doi":"10.1242/jcs.263844","DOIUrl":"10.1242/jcs.263844","url":null,"abstract":"Cytoplasmic dynein is essential in motor neurons for retrograde cargo transport that sustains neuronal connectivity. Little, however, is known about dynein function on the postsynaptic side of the circuit. Here, we report distinct postsynaptic roles for dynein at neuromuscular junctions in Drosophila. Intriguingly, we show that dynein puncta accumulate postsynaptically at glutamatergic synaptic terminals. Moreover, Skittles (Sktl), a phosphatidylinositol 4-phosphate 5-kinase that produces phosphatidylinositol 4,5-bisphosphate (PIP2) to organize the spectrin cytoskeleton, also localizes specifically to glutamatergic synaptic terminals. Depletion of postsynaptic dynein disrupted the accumulation of Skittles and the PIP2 phospholipid, and organization of the spectrin cytoskeleton at the postsynaptic membrane. Coincidental with dynein depletion, we observed an increase in the size of ionotropic glutamate receptor (iGluR) fields and an increase in the amplitude and frequency of miniature excitatory junctional potentials. PIP2 levels did not affect iGluR clustering, nor did dynein affect the levels of iGluR subunits at the neuromuscular junction. Our observations suggest a separate, transport-independent function for dynein in iGluR cluster organization. Based on the close apposition of dynein puncta to the iGluR fields, we speculate that dynein at the postsynaptic membrane contributes to the organization of the receptor fields, hence ensuring proper synaptic transmission.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046927","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

S. pombe Mis4 is required for exit from G0 as it is necessary for full nuclear separation during the subsequent M phase. 在静止的G0期，Schizosaccharomyces pombe Mis4确保在随后的M期完全的核分离。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-01 Epub Date: 2025-03-11 DOI: 10.1242/jcs.263747

Michiko Suma, Orie Arakawa, Yuria Tahara, Kenichi Sajiki, Shigeaki Saitoh, Mitsuhiro Yanagida

{"title":"S. pombe Mis4 is required for exit from G0 as it is necessary for full nuclear separation during the subsequent M phase.","authors":"Michiko Suma, Orie Arakawa, Yuria Tahara, Kenichi Sajiki, Shigeaki Saitoh, Mitsuhiro Yanagida","doi":"10.1242/jcs.263747","DOIUrl":"10.1242/jcs.263747","url":null,"abstract":"The evolutionarily conserved Mis4 protein establishes cohesion between replicated sister chromatids in vegetatively proliferating cells. In the fission yeast, Schizosaccharomyces pombe, defects in Mis4 lead to premature separation of sister chromatids, resulting in fatal chromosome mis-segregation during mitosis. In humans, NIPBL, an ortholog of Mis4, is responsible for a multisystem disorder called Cornelia de Lange syndrome. We have previously reported that Mis4 is also essential in non-proliferating quiescent cells. Whereas wild-type fission yeast cells can maintain high viability for long periods without cell division in the quiescent G0 phase, mis4-450 mutant cells cannot. Here, we show that Mis4 is not required for cells to enter G0 phase, but is essential for them to exit from it. When resuming mitosis after a passage of G0, mis4 mutant cells segregated sister chromatids successfully, but failed to separate daughter nuclei completely and consequently formed dikaryon-like cells. These findings suggest a novel role for Mis4/NIPBL in quiescent cells, which is a prerequisite for full nuclear separation upon resumed mitosis. As most human cells are in a quiescent state, this study might facilitate development of novel therapies for human diseases caused by Mis4/NIPBL deficiency.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364792","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