Pub Date : 2026-01-05Epub Date: 2025-12-05DOI: 10.1083/jcb.202501255
Dorival Mendes Rodrigues-Junior, Ana Rosa Sáez-Ibáñez, Takeshi Terabayashi, Nina Daubel, Taija Mäkinen, Olof Idevall-Hagren, Aristidis Moustakas, Ingvar Ferby
Receptor tyrosine kinases (RTKs) are important cargo in endocytic trafficking, yet their role in endosomal sorting and maturation of multivesicular bodies remains unclear. Here, we show that the ErbB3 (HER3) receptor sorts internalized Integrin β1 and the transferrin receptor, for endocytic recycling, in a manner that does not require ligand-induced ErbB3 signaling in breast epithelial cells. Loss of ErbB3 abrogates recycling of Integrin β1, likely from a Rab4-positive compartment, and redirects it toward lysosomal degradation or secretion as an extracellular vesicle (EV) cargo. ErbB3 depletion impairs the collective migration of breast epithelial cell sheets, coinciding with reduced cell-surface levels of Integrin β1 and increased release of Integrin β1-containing EVs. In contrast, EVs secreted from ErbB3-depleted cells enhance the motility of wild-type cells. Mechanistically, ErbB3 promotes assembly of the Arf6-GGA3-Rabaptin5 endosomal sorting complex to facilitate early recycling and suppress EV release. These findings provoke the notion that pseudo-RTKs play an active role in vesicular trafficking.
{"title":"Loss of ErbB3 redirects Integrin β1 from early endosomal recycling to secretion in extracellular vesicles.","authors":"Dorival Mendes Rodrigues-Junior, Ana Rosa Sáez-Ibáñez, Takeshi Terabayashi, Nina Daubel, Taija Mäkinen, Olof Idevall-Hagren, Aristidis Moustakas, Ingvar Ferby","doi":"10.1083/jcb.202501255","DOIUrl":"10.1083/jcb.202501255","url":null,"abstract":"<p><p>Receptor tyrosine kinases (RTKs) are important cargo in endocytic trafficking, yet their role in endosomal sorting and maturation of multivesicular bodies remains unclear. Here, we show that the ErbB3 (HER3) receptor sorts internalized Integrin β1 and the transferrin receptor, for endocytic recycling, in a manner that does not require ligand-induced ErbB3 signaling in breast epithelial cells. Loss of ErbB3 abrogates recycling of Integrin β1, likely from a Rab4-positive compartment, and redirects it toward lysosomal degradation or secretion as an extracellular vesicle (EV) cargo. ErbB3 depletion impairs the collective migration of breast epithelial cell sheets, coinciding with reduced cell-surface levels of Integrin β1 and increased release of Integrin β1-containing EVs. In contrast, EVs secreted from ErbB3-depleted cells enhance the motility of wild-type cells. Mechanistically, ErbB3 promotes assembly of the Arf6-GGA3-Rabaptin5 endosomal sorting complex to facilitate early recycling and suppress EV release. These findings provoke the notion that pseudo-RTKs play an active role in vesicular trafficking.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this issue, Teng et al. (https://doi.org/10.1083/jcb.202503070) use genome editing, classical tissue-specific gene knockouts, and live cell imaging to show that the interaction of p120ctn with the juxtamembrane domain of classical cadherins is necessary for tissue integrity during the cellular zippering required for upper lip formation in mammals.
{"title":"Keeping a stiff upper lip: p120ctn and tissue fusion.","authors":"Jeff Hardin","doi":"10.1083/jcb.202511015","DOIUrl":"https://doi.org/10.1083/jcb.202511015","url":null,"abstract":"In this issue, Teng et al. (https://doi.org/10.1083/jcb.202503070) use genome editing, classical tissue-specific gene knockouts, and live cell imaging to show that the interaction of p120ctn with the juxtamembrane domain of classical cadherins is necessary for tissue integrity during the cellular zippering required for upper lip formation in mammals.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"4 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate subcellular segmentation is crucial for understanding cellular processes, but traditional methods struggle with noise and complex structures. Convolutional neural networks improve accuracy but require large, time-consuming, and biased manually annotated datasets. We developed SynSeg, a pipeline generating synthetic training data for a U-Net model to segment subcellular structures, eliminating manual annotation. SynSeg leverages synthetic datasets with varied intensity, morphology, and signal distribution, delivering context-aware segmentations, even in challenging conditions. We demonstrate SynSeg's superior performance in segmenting vesicles and cytoskeletal filaments from cells and live Caenorhabditis elegans, outperforming traditional methods like Otsu's, ILEE, and FilamentSensor 2.0 and a recent deep learning method. Additionally, SynSeg effectively quantified disease-associated microtubule morphology in live cells, uncovering structural defects caused by mutant Tau proteins linked to neurodegeneration. Furthermore, SynSeg enables high-throughput, automated analysis, revealing that BSCL2 disease mutations increase lipid droplet size and showing its broad generalizability for quantitative cell biology. These results highlight the potential of synthetic data to advance biological segmentation.
{"title":"SynSeg: A synthetic data-driven approach for robust subcellular structure segmentation.","authors":"Zhengyang Guo,Zi Wang,Zihan Chen,Kaiming Xu,Yongping Chai,Jingyi Ke,Jingwen Huang,Yuqi Ye,Hui Wang,Jinxiang Zhang,Guangshuo Ou","doi":"10.1083/jcb.202506096","DOIUrl":"https://doi.org/10.1083/jcb.202506096","url":null,"abstract":"Accurate subcellular segmentation is crucial for understanding cellular processes, but traditional methods struggle with noise and complex structures. Convolutional neural networks improve accuracy but require large, time-consuming, and biased manually annotated datasets. We developed SynSeg, a pipeline generating synthetic training data for a U-Net model to segment subcellular structures, eliminating manual annotation. SynSeg leverages synthetic datasets with varied intensity, morphology, and signal distribution, delivering context-aware segmentations, even in challenging conditions. We demonstrate SynSeg's superior performance in segmenting vesicles and cytoskeletal filaments from cells and live Caenorhabditis elegans, outperforming traditional methods like Otsu's, ILEE, and FilamentSensor 2.0 and a recent deep learning method. Additionally, SynSeg effectively quantified disease-associated microtubule morphology in live cells, uncovering structural defects caused by mutant Tau proteins linked to neurodegeneration. Furthermore, SynSeg enables high-throughput, automated analysis, revealing that BSCL2 disease mutations increase lipid droplet size and showing its broad generalizability for quantitative cell biology. These results highlight the potential of synthetic data to advance biological segmentation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"5 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this issue, Ryken et al. (https://doi.org/10.1083/jcb.202506021) show that three Ca2+ pumps (ACAs) play an important role in the maintenance of the tip-focused Ca2+ gradient in moss tip-growing cells. The steepness of this gradient promotes the secretion of the new cell material needed for tip growth.
{"title":"A crucial step toward understanding tip growth in plants.","authors":"Ivan Radin","doi":"10.1083/jcb.202510221","DOIUrl":"https://doi.org/10.1083/jcb.202510221","url":null,"abstract":"In this issue, Ryken et al. (https://doi.org/10.1083/jcb.202506021) show that three Ca2+ pumps (ACAs) play an important role in the maintenance of the tip-focused Ca2+ gradient in moss tip-growing cells. The steepness of this gradient promotes the secretion of the new cell material needed for tip growth.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"32 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Jacqmin,Florentine Gilis,Martine Albert,Jean-François Gaussin,Michel Jadot,Marielle Boonen
Spastic paraplegia 21 is a neurodegenerative disease characterized by the degeneration of corticospinal axons. It is caused by mutations in the SPG21 gene, which encodes maspardin, a cytosolic protein of unknown function that associates with the late endosomal/lysosomal membrane. Intriguingly, we found that the phosphorylation level of the transcription factor EB (TFEB), a master regulator of the CLEAR gene network, is decreased in SPG21 knockout cells, leading to TFEB nuclear translocation. Our investigations revealed that the Rag-mediated presentation of TFEB to the mTOR kinase and its subsequent phosphorylation is disturbed by a delocalization of the RAB7 GTPase, a maspardin-binding partner, from retromer-positive late endosomes to lysosomes. This redistribution decreases the interaction between RAB7 and its GTPase-activating protein (GAP), TBC1D5. Consequently, RAB7 remains primarily GTP-bound, recruiting more FYCO1 to lysosomes and promoting the anterograde movement of these organelles along microtubules. These findings identify maspardin as a newly discovered RAB7 effector and shed light on several consequences of its deficiency.
{"title":"Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.","authors":"Thomas Jacqmin,Florentine Gilis,Martine Albert,Jean-François Gaussin,Michel Jadot,Marielle Boonen","doi":"10.1083/jcb.202501135","DOIUrl":"https://doi.org/10.1083/jcb.202501135","url":null,"abstract":"Spastic paraplegia 21 is a neurodegenerative disease characterized by the degeneration of corticospinal axons. It is caused by mutations in the SPG21 gene, which encodes maspardin, a cytosolic protein of unknown function that associates with the late endosomal/lysosomal membrane. Intriguingly, we found that the phosphorylation level of the transcription factor EB (TFEB), a master regulator of the CLEAR gene network, is decreased in SPG21 knockout cells, leading to TFEB nuclear translocation. Our investigations revealed that the Rag-mediated presentation of TFEB to the mTOR kinase and its subsequent phosphorylation is disturbed by a delocalization of the RAB7 GTPase, a maspardin-binding partner, from retromer-positive late endosomes to lysosomes. This redistribution decreases the interaction between RAB7 and its GTPase-activating protein (GAP), TBC1D5. Consequently, RAB7 remains primarily GTP-bound, recruiting more FYCO1 to lysosomes and promoting the anterograde movement of these organelles along microtubules. These findings identify maspardin as a newly discovered RAB7 effector and shed light on several consequences of its deficiency.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"5 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aya Ben-Hamo-Arad,Neven Serhan,Lilach Porat-Kuperstein,Boris Shklyar,Lilach Simchi,Alina Kolpakova,Eli Arama,Hila Toledano
Somatic cells in both mammalian and Drosophila testes perform diverse roles in regulating germline stem cell differentiation into sperm. Beyond their supportive functions, such as encapsulation and signaling, somatic cells also act as tissue-resident, non-professional phagocytes. In Drosophila testis, somatic cyst cells eliminate approximately a quarter of newly emerged spermatogonial progenitors, a role seemingly contradictory to their supportive function. Here, we examined individual events in which cyst cells alternated between supporting germ cells and promoting their death, revealing distinct morphological features. Our data indicate that, in addition to well-defined cyst cells derived from stem cell divisions and escorting differentiating spermatogonia, a distinct population of long-lived steady cyst cells arises during larval development. These steady cyst cells persist at the apical tip of the testis for extended periods and engage in phagoptosis. This distinction separates cyst cells into two subpopulations based on function and morphology, highlighting how genetically similar cells adopt specialized roles depending on their developmental origin and timing.
{"title":"Steady and escort cyst cells regulate Drosophila germline stem cell differentiation and death.","authors":"Aya Ben-Hamo-Arad,Neven Serhan,Lilach Porat-Kuperstein,Boris Shklyar,Lilach Simchi,Alina Kolpakova,Eli Arama,Hila Toledano","doi":"10.1083/jcb.202501134","DOIUrl":"https://doi.org/10.1083/jcb.202501134","url":null,"abstract":"Somatic cells in both mammalian and Drosophila testes perform diverse roles in regulating germline stem cell differentiation into sperm. Beyond their supportive functions, such as encapsulation and signaling, somatic cells also act as tissue-resident, non-professional phagocytes. In Drosophila testis, somatic cyst cells eliminate approximately a quarter of newly emerged spermatogonial progenitors, a role seemingly contradictory to their supportive function. Here, we examined individual events in which cyst cells alternated between supporting germ cells and promoting their death, revealing distinct morphological features. Our data indicate that, in addition to well-defined cyst cells derived from stem cell divisions and escorting differentiating spermatogonia, a distinct population of long-lived steady cyst cells arises during larval development. These steady cyst cells persist at the apical tip of the testis for extended periods and engage in phagoptosis. This distinction separates cyst cells into two subpopulations based on function and morphology, highlighting how genetically similar cells adopt specialized roles depending on their developmental origin and timing.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"59 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As cells contract and reshape to enable tissue morphogenesis, their own internal structures can constrain these behaviors. In the Drosophila germband, the uncrowding of nuclei away from an initially common plane is required for efficient cell intercalation and extension. Here, we find that a centrosomally derived microtubule network transitions into non-centrosomal arrays that are deeply embedded in nuclei before shifting towards the apical cortex as GBE progresses. Disrupting ncMT function by compromising CLASP or Patronin function leads to failures in nuclear dispersion and results in MT networks dominated by centrosomal arrays. CLASP disruption also causes a marked detachment of MTs from nuclei, severely affecting nuclear orientation and dispersion. Our results also reveal a fundamental antagonism between ncMT and centrosomal networks-an observation corroborated in γ-tubulin embryos. Lastly, EB1 disruption blocks the apical shift of ncMTs, leading to dispersion defects. Overall, our findings reveal that nuclear repositioning during epithelial remodeling depends on a centrosome-to-ncMT transition requiring CLASP, EB1, and Patronin function.
{"title":"Perinuclear non-centrosomal microtubules direct nuclei dispersion during epithelial morphogenesis.","authors":"Rashmi Budhathoki,Liam J Russell,Dinah Loerke,J Todd Blankenship","doi":"10.1083/jcb.202507117","DOIUrl":"https://doi.org/10.1083/jcb.202507117","url":null,"abstract":"As cells contract and reshape to enable tissue morphogenesis, their own internal structures can constrain these behaviors. In the Drosophila germband, the uncrowding of nuclei away from an initially common plane is required for efficient cell intercalation and extension. Here, we find that a centrosomally derived microtubule network transitions into non-centrosomal arrays that are deeply embedded in nuclei before shifting towards the apical cortex as GBE progresses. Disrupting ncMT function by compromising CLASP or Patronin function leads to failures in nuclear dispersion and results in MT networks dominated by centrosomal arrays. CLASP disruption also causes a marked detachment of MTs from nuclei, severely affecting nuclear orientation and dispersion. Our results also reveal a fundamental antagonism between ncMT and centrosomal networks-an observation corroborated in γ-tubulin embryos. Lastly, EB1 disruption blocks the apical shift of ncMTs, leading to dispersion defects. Overall, our findings reveal that nuclear repositioning during epithelial remodeling depends on a centrosome-to-ncMT transition requiring CLASP, EB1, and Patronin function.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"10 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michal Shahar,Alia Qasem,Eshkar Shamay,Amanda Tissawak,Yariv Maron,Anat Florentin
The apicoplast organelle of the malaria parasite, Plasmodium falciparum, is essential for parasite replication, though its cell cycle regulation remains poorly understood. We developed a dynamic live-imaging platform with analytical capabilities to track subcellular structures throughout the parasite's 48-h intraerythrocytic life cycle. Our analysis revealed four distinct morphological stages in apicoplast development that correlate with nuclear replication. We identified a critical "Crown" morphology stage required for nucleus-apicoplast attachment, where the apicoplast stretches across multiple nuclei, in close association with centriolar plaques. We measured DNA ploidy and replication dynamics of the nuclear and apicoplast genomes. Inhibition of nuclear DNA replication blocked apicoplast biogenesis at early stages, demonstrating dependence on S-phase initiation. Conversely, inhibiting apicoplast genome replication minimally affected organelle development but disrupted the Crown stage, preventing proper organelle segregation into daughter cells. These findings establish a central pathway connecting apicoplast development to the cell cycle and an independent mechanism governing organelle inheritance.
{"title":"Independent nuclear and organellar mechanisms determine apicoplast fate in malaria parasites.","authors":"Michal Shahar,Alia Qasem,Eshkar Shamay,Amanda Tissawak,Yariv Maron,Anat Florentin","doi":"10.1083/jcb.202504052","DOIUrl":"https://doi.org/10.1083/jcb.202504052","url":null,"abstract":"The apicoplast organelle of the malaria parasite, Plasmodium falciparum, is essential for parasite replication, though its cell cycle regulation remains poorly understood. We developed a dynamic live-imaging platform with analytical capabilities to track subcellular structures throughout the parasite's 48-h intraerythrocytic life cycle. Our analysis revealed four distinct morphological stages in apicoplast development that correlate with nuclear replication. We identified a critical \"Crown\" morphology stage required for nucleus-apicoplast attachment, where the apicoplast stretches across multiple nuclei, in close association with centriolar plaques. We measured DNA ploidy and replication dynamics of the nuclear and apicoplast genomes. Inhibition of nuclear DNA replication blocked apicoplast biogenesis at early stages, demonstrating dependence on S-phase initiation. Conversely, inhibiting apicoplast genome replication minimally affected organelle development but disrupted the Crown stage, preventing proper organelle segregation into daughter cells. These findings establish a central pathway connecting apicoplast development to the cell cycle and an independent mechanism governing organelle inheritance.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"110 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kun Gao,Ruiya Shi,Chenying Xu,Zhaoyang Mao,Changying Guo,Liang Jin
DNA damage repair is vital for maintaining genetic stability and integrity of cells that encounter DNA-damaging agents. So far, a series of multifunctional proteins and long noncoding RNAs (lncRNAs) have been demonstrated to participate in the DNA damage response (DDR). However, our current understanding of detailed mechanisms of DNA damage repair remains limited. Herein, we report that lncRNA EGFR-AS1 is functionally involved in DDR in both non-small-cell lung cancer cells and noncancerous cells. Using DNA repair reporter, we found that EGFR-AS1 overexpression significantly enhances the efficiency of both the classical nonhomologous end-joining and homologous recombination pathways. Through the lncRNA interactome, we identified a set of DNA repair factors, including the canonical DNA damage sensor PARP1 and NAD+ supplier NMNAT1. Upon DNA damage, DNA-activated PARP1 binds to EGFR-AS1 and forms a ternary complex with NMNAT1, promoting NAD+ utilization and poly(ADP-ribosyl)ation (PARylation) of PARP1. Additionally, EGFR-AS1 also facilitates displacing PARP1 from the sites of damaged DNA. Our findings demonstrate a lncRNA-associated PARP1 activation and displacement in DDR and highlight the potential of EGFR-AS1 as a target for cancer therapy.
{"title":"lncRNA EGFR-AS1 promotes DNA damage repair by enhancing PARP1-mediated PARylation.","authors":"Kun Gao,Ruiya Shi,Chenying Xu,Zhaoyang Mao,Changying Guo,Liang Jin","doi":"10.1083/jcb.202501091","DOIUrl":"https://doi.org/10.1083/jcb.202501091","url":null,"abstract":"DNA damage repair is vital for maintaining genetic stability and integrity of cells that encounter DNA-damaging agents. So far, a series of multifunctional proteins and long noncoding RNAs (lncRNAs) have been demonstrated to participate in the DNA damage response (DDR). However, our current understanding of detailed mechanisms of DNA damage repair remains limited. Herein, we report that lncRNA EGFR-AS1 is functionally involved in DDR in both non-small-cell lung cancer cells and noncancerous cells. Using DNA repair reporter, we found that EGFR-AS1 overexpression significantly enhances the efficiency of both the classical nonhomologous end-joining and homologous recombination pathways. Through the lncRNA interactome, we identified a set of DNA repair factors, including the canonical DNA damage sensor PARP1 and NAD+ supplier NMNAT1. Upon DNA damage, DNA-activated PARP1 binds to EGFR-AS1 and forms a ternary complex with NMNAT1, promoting NAD+ utilization and poly(ADP-ribosyl)ation (PARylation) of PARP1. Additionally, EGFR-AS1 also facilitates displacing PARP1 from the sites of damaged DNA. Our findings demonstrate a lncRNA-associated PARP1 activation and displacement in DDR and highlight the potential of EGFR-AS1 as a target for cancer therapy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"1 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentine Thomas,Hikari Mase,Laetitia Michon,Andrea Picco,Marko Kaksonen,Sophie G Martin
Many processes such as polarized growth and secretion require specific actin networks. In fungi, cell-cell fusion requires cell wall digestion mediated by local secretion of lytic enzymes. In Schizosaccharomyces pombe, the myosin V Myo52 transports enzyme-containing secretory vesicles on the actin fusion focus, an aster-like actin network assembled by the condensate-forming formin Fus1. The fusion focus also concentrates proteins regulating cell polarity, communication, cytoskeleton, exocytosis, and membrane merging. Here, using centroid tracking and averaging, we present a spatiotemporal map of the fusion site with 8-nm precision. We show that a pool of vesicles remains at constant distance from the membrane as the actin structure condenses. Unexpectedly, Myo52 detaches from this pool and colocalizes with Fus1 closer to the membrane. We show that Myo52 binds Fus1 and transports it along actin filaments, and that Myo52 and Fus1 actin assembly activity contribute to focus compaction. Thus, myosin V-driven transport of formin Fus1 along Fus1-nucleated actin filaments underlies positive feedback for actin aster formation.
{"title":"High-resolution mapping of the actin fusion focus reveals myosin V-dependent formin transport for aster formation.","authors":"Valentine Thomas,Hikari Mase,Laetitia Michon,Andrea Picco,Marko Kaksonen,Sophie G Martin","doi":"10.1083/jcb.202510018","DOIUrl":"https://doi.org/10.1083/jcb.202510018","url":null,"abstract":"Many processes such as polarized growth and secretion require specific actin networks. In fungi, cell-cell fusion requires cell wall digestion mediated by local secretion of lytic enzymes. In Schizosaccharomyces pombe, the myosin V Myo52 transports enzyme-containing secretory vesicles on the actin fusion focus, an aster-like actin network assembled by the condensate-forming formin Fus1. The fusion focus also concentrates proteins regulating cell polarity, communication, cytoskeleton, exocytosis, and membrane merging. Here, using centroid tracking and averaging, we present a spatiotemporal map of the fusion site with 8-nm precision. We show that a pool of vesicles remains at constant distance from the membrane as the actin structure condenses. Unexpectedly, Myo52 detaches from this pool and colocalizes with Fus1 closer to the membrane. We show that Myo52 binds Fus1 and transports it along actin filaments, and that Myo52 and Fus1 actin assembly activity contribute to focus compaction. Thus, myosin V-driven transport of formin Fus1 along Fus1-nucleated actin filaments underlies positive feedback for actin aster formation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"4 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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