Journal of cell science最新文献_第4页

Cell biology meets climate resilience - a call to action.

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

γ-tubulin mediates DNA double-strand break repair.

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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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.

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

Cell compression - relevance, mechanotransduction mechanisms and tools.

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

Formin 3 stabilizes the cytoskeleton of Drosophila tendon cells, thus enabling them to resist muscle tensile forces.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-14 DOI: 10.1242/jcs.263543

Helena Pissarek, Na Huang, Leanna H Frasch, Hermann Aberle, Manfred Frasch

{"title":"Formin 3 stabilizes the cytoskeleton of Drosophila tendon cells, thus enabling them to resist muscle tensile forces.","authors":"Helena Pissarek, Na Huang, Leanna H Frasch, Hermann Aberle, Manfred Frasch","doi":"10.1242/jcs.263543","DOIUrl":"https://doi.org/10.1242/jcs.263543","url":null,"abstract":"The cytoskeleton of Drosophila tendon cells features specialized F-actin/microtubule arrays that endow these cells with resistance to the tensile forces exerted by the attached muscles. In a forward genetic screen for mutants with neuromuscular junction and muscle morphology phenotypes in larvae, we identified formin 3 (form3) as a crucial component for stabilizing these cytoskeletal arrays under muscle tension. form3 mutants exhibit severely stretched tendon cells in contact with directly attached larval body wall muscles, leading to muscle retraction and rounding. Both the actomyosin and microtubule arrays are expanded likewise in these mutants and can separate laterally in extreme cases. The analysis of a natively HA-tagged, functional version of Form3 reveals that Form3 is distributed along the length of these cytoskeletal arrays. Based on our findings and existing data on vertebrate and C. elegans orthologs of form3, we propose that Form3's primary function in this context is to co-bundle actin filaments and microtubules, thus maximizing the rigidity of these cytoskeletal structures against muscle tensile forces.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624881","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

A dual-purification system to isolate mitochondrial subpopulations.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-13 DOI: 10.1242/jcs.263693

Corey N Cunningham, Jonathan G Van Vranken, Jakeline Larios, Katarina Heyden, Steven P Gygi, Jared Rutter

{"title":"A dual-purification system to isolate mitochondrial subpopulations.","authors":"Corey N Cunningham, Jonathan G Van Vranken, Jakeline Larios, Katarina Heyden, Steven P Gygi, Jared Rutter","doi":"10.1242/jcs.263693","DOIUrl":"https://doi.org/10.1242/jcs.263693","url":null,"abstract":"Mitochondria perform diverse functions, such as producing ATP through oxidative phosphorylation, synthesizing macromolecule precursors, maintaining redox balance, and many others. Given this diversity of functions, we and others have hypothesized that cells maintain specialized subpopulations of mitochondria. To begin addressing this hypothesis, we developed a new dual-purification system to isolate subpopulations of mitochondria for chemical and biochemical analyses. We used APEX2 proximity labeling such that mitochondria were biotinylated based on proximity to another organelle. All mitochondria were isolated by an elutable MitoTag-based affinity precipitation system. Biotinylated mitochondria were then purified using immobilized avidin. We used this system to compare the proteomes of endosome- and lipid droplet-associated mitochondria in U-2 OS cells, which demonstrated that these subpopulations were indistinguishable from one another but were distinct from the global mitochondria proteome. Our results suggest that this purification system could aid in describing subpopulations that contribute to intracellular mitochondrial heterogeneity, and that this heterogeneity might be more substantial than previously imagined.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615564","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

Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-11 DOI: 10.1242/jcs.263487

Yuki Ishii, Jessica C Orr, Marie-Belle El Mdawar, Denise R Bairros de Pilger, David R Pearce, Kyren A Lazarus, Rebecca E Graham, Marko Z Nikolić, Robin Ketteler, Neil O Carragher, Sam M Janes, Robert E Hynds

{"title":"Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies.","authors":"Yuki Ishii, Jessica C Orr, Marie-Belle El Mdawar, Denise R Bairros de Pilger, David R Pearce, Kyren A Lazarus, Rebecca E Graham, Marko Z Nikolić, Robin Ketteler, Neil O Carragher, Sam M Janes, Robert E Hynds","doi":"10.1242/jcs.263487","DOIUrl":"https://doi.org/10.1242/jcs.263487","url":null,"abstract":"Regeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. The mechanisms regulating the proliferation and differentiation of tissue-resident airway basal stem cells remain incompletely understood. To identify compounds that promote human airway basal cell proliferation, we performed phenotype-based compound screening of 1,429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase. 17 pro-proliferative compounds were validated in independent donor cell cultures, including the antiretroviral therapy abacavir and several Wnt signalling pathway activating compounds. The effects of compounds on proliferation were further explored in colony formation and 3D organoid assays. Structurally and functionally-related compounds that more potently induced Wnt pathway activation were investigated. One such compound, 1-azakenpaullone, induced Wnt target gene activation and basal cell proliferation in mice. Our results demonstrate the pro-proliferative effect of small-molecule Wnt pathway activators on airway basal cells. These findings contribute to the rationale to develop novel approaches to modulate Wnt signalling during airway epithelial repair.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597050","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

S. pombe Mis4 is required for exit from G0 as it is necessary for full nuclear separation during the subsequent M phase.

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

Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.

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

Ground-state pluripotent stem cells are characterized by Rac1-dependent cadherin-enriched F-actin complexes.

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.263811

Shiying Liu, Yue Meng, Xi Lan, Rong Li, Pakorn Kanchanawong

{"title":"Ground-state pluripotent stem cells are characterized by Rac1-dependent cadherin-enriched F-actin complexes.","authors":"Shiying Liu, Yue Meng, Xi Lan, Rong Li, Pakorn Kanchanawong","doi":"10.1242/jcs.263811","DOIUrl":"10.1242/jcs.263811","url":null,"abstract":"Pluripotent stem cells (PSCs) exhibit extraordinary differentiation potential and are thus highly valuable cellular model systems. However, although different PSC types corresponding to distinct stages of embryogenesis have been in common use, aspects of their cellular architecture and mechanobiology remain insufficiently understood. Here, we investigated how the actin cytoskeleton is regulated in different pluripotency states. We observed a drastic reorganization during the transition from ground-state naïve mouse embryonic stem cells (mESCs) into converted prime epiblast stem cells (EpiSCs). mESCs are characterized by prominent actin-enriched cortical structures that contain cadherin-based cell-cell junctional components, despite not locating at cell-cell junctions. We term these structures 'non-junctional cadherin complexes' (NJCCs) and show that they are under low mechanical tension, depend on the ectodomain but not the cytoplasmic domain of E-cadherin, and exhibit minimal Ca2+ dependence. Active Rac1 was identified as a negative regulator that promotes β-catenin dissociation and NJCC fragmentation. Our data suggests that NJCCs might arise from the cis-association of E-cadherin ectodomain, with potential roles in ground-state pluripotency, and could serve as structural markers to distinguish heterogeneous population of pluripotent stem cells.","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":"143065971","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