Journal of cell science最新文献_第4页

Contribution of topoisomerase IIα chromatin-tether and C-terminal domain to mitotic chromosome association and structural organization. 拓扑异构酶ⅱα染色质链和c端结构域对有丝分裂染色体结合和结构组织的贡献。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-15 Epub Date: 2026-10-29 DOI: 10.1242/jcs.264838

Bunu Lama, Sanjana Sundararajan, Anita Saraf, Hyewon Park, Asbin Chand, Regan Krueger, Tomoko Saito-Fujita, Noriko Saitoh, Shinji Kawano, Duncan J Clarke, Yoshiaki Azuma

{"title":"Contribution of topoisomerase IIα chromatin-tether and C-terminal domain to mitotic chromosome association and structural organization.","authors":"Bunu Lama, Sanjana Sundararajan, Anita Saraf, Hyewon Park, Asbin Chand, Regan Krueger, Tomoko Saito-Fujita, Noriko Saitoh, Shinji Kawano, Duncan J Clarke, Yoshiaki Azuma","doi":"10.1242/jcs.264838","DOIUrl":"10.1242/jcs.264838","url":null,"abstract":"Mitotic functions of topoisomerase IIα (TopoIIα) are dictated by its C-terminal domain (CTD), which is distinct from that of TopoIIβ. The chromatin-tether (ChT) domain within the αCTD recognizes methylated chromatin, an ability lacking for TopoIIβ, and loss of αChT leads to the formation of ultrafine DNA bridges (UFBs) and chromosome bridges in anaphase. Because UFBs arise from incomplete decatenation of tangled genomic DNA, these observations suggest that αChT directs TopoIIα to sites of tangled DNA. Here, by chimeric swapping of ChT domains between the isoforms in AID-TopoIIα DLD1 cells, TopoIIα-βChT and TopoIIβ-αChT, we reveal that αChT improves the ability of TopoIIβ with respect to UFB resolution and does not prevent chromosome bridges. This highlights the requirement for a complete αCTD for accurate chromosome segregation. Salt extraction assays show that the full αCTD is required for stable TopoIIα association with mitotic chromosomes, while the αChT enhances this association without affecting decatenation activity. Moreover, proteomic analysis showed altered levels of condensin and centromeric proteins in TopoII mutants. These results reveal the role of αChT in the αCTD-dependent chromosomal targeting mechanism of TopoIIα as well as an αChT-dependent requirement for robust structural organization of mitotic chromosomes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110272","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

Two-step regulation of bouquet formation by mating pheromone signaling and Pat1 activity reduction during fission yeast meiosis. 裂变酵母减数分裂过程中交配信息素信号和Pat1活性降低对花束形成的两步调控。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-14 DOI: 10.1242/jcs.264805

Alimul Islam, Shinnosuke Kawai, Ayumu Yamamoto

{"title":"Two-step regulation of bouquet formation by mating pheromone signaling and Pat1 activity reduction during fission yeast meiosis.","authors":"Alimul Islam, Shinnosuke Kawai, Ayumu Yamamoto","doi":"10.1242/jcs.264805","DOIUrl":"https://doi.org/10.1242/jcs.264805","url":null,"abstract":"Upon meiosis initiation in the fission yeast Schizosaccharomyces pombe, centromeres detach from the spindle pole body (SPB), while telomeres cluster at the SPB, forming the bouquet, which promotes homologous chromosome pairing. Bouquet formation is regulated by mating pheromone signaling and Pat1 kinase, a central regulator of meiosis. Centromere detachment also requires telomere clustering-dependent SPB recruitment of the telomere component Taz1. However, the precise underlying regulatory mechanisms remain unclear. Here, using a haploid cell system that allows synchronous meiosis induction, we show that mating pheromone signaling induces transient bouquet formation, whereas bouquet maintenance additionally requires Pat1 activity reduction, which normally occurs after conjugation. Furthermore, impairment of telomere clustering inhibits centromere detachment regardless of Pat1 activity reduction, whereas SPB-recruited Taz1 restores centromere detachment only when Pat1 activity is reduced. Thus, bouquet formation proceeds in two steps: a transient establishment step dependent on mating pheromone signaling, followed by a maintenance step requiring Pat1 activity reduction and SPB recruitment of Taz1. We propose that this regulation enables rapid cell cycle resumption upon nutrient replenishment in unconjugated cells, while ensuring meiotic commitment in conjugated cells.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182039","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

Visualisation of the regulation of CDK/cyclin complexes by p21 (CDKN1A) in living cells using FLIM-FRET. 利用flm - fret可视化活细胞中p21 （CDKN1A）对CDK/cyclin复合物的调控。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-14 DOI: 10.1242/jcs.265097

Christian Melle, Birgit Hoffmann, Annett Wiesenburg, Christoph Biskup

{"title":"Visualisation of the regulation of CDK/cyclin complexes by p21 (CDKN1A) in living cells using FLIM-FRET.","authors":"Christian Melle, Birgit Hoffmann, Annett Wiesenburg, Christoph Biskup","doi":"10.1242/jcs.265097","DOIUrl":"https://doi.org/10.1242/jcs.265097","url":null,"abstract":"The cell cycle is controlled in G1-phase by activities of three cyclin-dependent kinases (CDKs), CDK4/6 and CDK2, and their regulatory partners, cyclin D and cyclin E, respectively. p21 (CDKN1A), a member of the KIP/CIP family, is involved in regulation of CDK/cyclin complexes. In the present study, we analysed the impact of p21 on CDK/cyclin complex formation in living cells by fluorescence lifetime imaging microscopy (FLIM)-based Förster resonance energy transfer (FRET) measurements. Depending on the additional expression of p21, both CDK4/cyclin D3 and CDK2/cyclin E1 interactions have been favoured reflected by increased FRET efficiencies (E). Furthermore, post-translational modifications (PTM) as well as the redox status of p21 can regulate the impact on CDK/cyclin complexes. We show that phosphorylation-mimicking mutants of p21 seem to be able to affect the CDK/cyclin protein-protein interactions (PPIs), and that the reduced p21C41S variant decreased binding between CDK4 and cyclin D3. In contrast, p21C41S increased the CDK2/cyclin E1 interaction such as wild-type p21. Hence, wild-type p21 and its specific variants have an impact on the formation of distinct CDK/cyclin complexes under physiological conditions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182054","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

FRET imaging of ERK activity in an orthotopic xenograft model of patient-derived pancreatic ductal adenocarcinoma using imaging window. 利用成像窗对患者源性胰腺导管腺癌原位异种移植模型中ERK活性的FRET成像。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-09 DOI: 10.1242/jcs.265075

Houssam Al-Koussa, Daisuke Taniguchi, Masafumi Kuroda, Yukino Inomata, Ye Huaze, Akihito Machinaga, Nobuyuki Kakiuchi, Seishi Ogawa, Hiroshi Seno, Shigeki Higashiyama, Michiyuki Matsuda, Toru Hiratsuka

{"title":"FRET imaging of ERK activity in an orthotopic xenograft model of patient-derived pancreatic ductal adenocarcinoma using imaging window.","authors":"Houssam Al-Koussa, Daisuke Taniguchi, Masafumi Kuroda, Yukino Inomata, Ye Huaze, Akihito Machinaga, Nobuyuki Kakiuchi, Seishi Ogawa, Hiroshi Seno, Shigeki Higashiyama, Michiyuki Matsuda, Toru Hiratsuka","doi":"10.1242/jcs.265075","DOIUrl":"https://doi.org/10.1242/jcs.265075","url":null,"abstract":"Intravital imaging of cancer xenograft models enables the observation of cells in their tissue microenvironment. Application of molecular activity probes to intravital imaging, however, often poses technical difficulties. Here we sought to visualize Extracellular signal-regulated kinase (ERK) activity in an orthotopic xenograft model of pancreatic cancer. Our custom-made pancreatic imaging window (PIW) enabled long-term tracking (> 2 weeks) of cancer xenografts showing heterogeneous growth potential. Our validation approach of Förster resonance energy transfer (FRET) imaging by a kinase-dead mutant ERK biosensor suggested the local pH may affect the ratiometric interpretation of FRET efficiency. Nevertheless, our FRET analysis allowed to detect pharmacological inhibition of ERK activity, which supports the validity of the experimental model to dissect heterogeneous drug responses of cancer cells in their microenvironment. Of note, we found that collagen signal was negatively correlated with local ERK activity heterogeneity, highlighting the benefit of our imaging system to observe the intricate pharmacodynamics modified by fibrosis. Our intravital live imaging platform paves the way for a novel pre-clinical model that links the molecular dynamics to the living tissue environment of pancreatic cancer.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136778","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 phosphoinositide and RAB switch controls early macropinocytosis. 磷酸肌肽和RAB开关控制早期巨噬细胞增多症。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-09 DOI: 10.1242/jcs.265349

Hélène Spangenberg, Emilie Løgith Moe, Øyvind Ødegård Fougner, Marte Sneeggen, Meng Pan, Kia Wee Tan, Maria Mateo Tortola, Camila Valenzuela, Yuen-Yan Chang, Harald Stenmark, Camilla Raiborg, Kay Oliver Schink

{"title":"A phosphoinositide and RAB switch controls early macropinocytosis.","authors":"Hélène Spangenberg, Emilie Løgith Moe, Øyvind Ødegård Fougner, Marte Sneeggen, Meng Pan, Kia Wee Tan, Maria Mateo Tortola, Camila Valenzuela, Yuen-Yan Chang, Harald Stenmark, Camilla Raiborg, Kay Oliver Schink","doi":"10.1242/jcs.265349","DOIUrl":"https://doi.org/10.1242/jcs.265349","url":null,"abstract":"Macropinocytosis is a non-selective endocytic process by which cells take up large amounts of extracellular fluid into giant vesicles known as macropinosomes. This mechanism is used by immune cells to sample the surroundings for antigens and can be exploited by cancer cells for nutrient uptake. What determines macropinosome fate after internalization is largely unknown. Here we investigate the role of the phosphatidylinositol 3-kinase VPS34/PIK3C3 and its product phosphatidylinositol 3-phosphate (PtdIns3P) in macropinosome fate determination. VPS34 inhibition reduced successful macropinosome maturation and fluid-phase uptake and prevented recruitment of early endosomal factors, including the small GTPase RAB5A and its effectors, to forming macropinosomes. Instead, forming macropinosomes under VPS34 inhibition accumulated regulators of endocytic recycling, including RAB8A, RAB10, RAB11A, and PtdIns4P, which led to fusion of macropinosomes with the plasma membrane. Whereas RAB5A was critical for establishment of endosomal identity, macropinosome fusion with the plasma membrane depended on RAB8A. Thus, macropinosome maturation is regulated by a VPS34-dependent phosphoinositide and RAB transition that determines whether newly formed macropinosomes acquire endosomal identity or recycle to the plasma membrane.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136806","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 distinct interphase microtubule state marks host cell permissiveness to Chlamydia pneumoniae entry. 明显的间期微管状态标志着宿主细胞允许肺炎衣原体进入。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265369

Katharina Schenk, Johannes Hegemann, Ursula Fleig

{"title":"A distinct interphase microtubule state marks host cell permissiveness to Chlamydia pneumoniae entry.","authors":"Katharina Schenk, Johannes Hegemann, Ursula Fleig","doi":"10.1242/jcs.265369","DOIUrl":"https://doi.org/10.1242/jcs.265369","url":null,"abstract":"Entry of intracellular pathogenic bacteria is widely considered an actin-driven process, potentially overlooking contributions of the microtubule cytoskeleton. Interphase microtubules exist in distinct states, but whether this heterogeneity influences bacterial entry is unknown. Here, using the obligate intracellular bacterium Chlamydia pneumoniae, we show that microtubules not only contribute to bacterial entry but that their pre-existing state influences host-cell permissiveness. Cells enriched in acetylated microtubules are preferentially infected, whereas detyrosinated microtubules show no such association. Taxol enhances entry, whereas selective elevation of microtubule acetylation with Tubacin does not, indicating that acetylation itself is insufficient and pointing instead to a permissive state associated with stabilized, long-lived microtubules. We next show that this relationship is reciprocal: infection induces a dose-dependent increase in microtubule acetylation that requires bacterial viability and is not reproduced by uptake of Yersinia pseudotuberculosis Invasin-coated beads, indicating that internalization alone is insufficient to trigger this response. Finally, to examine how early chlamydial proteins can alter microtubule behaviour, we assessed the effect of the secreted TarP-family actin-microtubule regulator CPn0572 on microtubule stability. In the Schizosaccharomyces pombe in vivo test system, CPn0572 promotes microtubule persistence and can act together with another chlamydial microtubule modulator to generate a combined microtubule phenotype. Together, these findings identify the pre-existing microtubule state as a determinant of Chlamydia pneumoniae entry, show that infection subsequently remodels the microtubule cytoskeleton, and demonstrate that an early chlamydial protein can directly alter microtubule behaviour.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127572","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

Insulin-stimulated phosphorylation of CLASP2 by ERK regulates microtubule plus-end binding of CLASP2 and insulin-regulated microtubule stabilization. 胰岛素刺激下ERK对CLASP2的磷酸化调节了CLASP2的微管+端结合和胰岛素调节的微管稳定。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265004

James Krantz, DeHaven McCrary, Natalie K Barker, Sara S Parker, April Mengos, Mackenzie Roman, Skylar R Batty, Atley P Moberly, Corbin Jensen, Noel Warfel, Ghassan Mouneimne, Nam Y Lee, Lawrence J Mandarino, Paul R Langlais

{"title":"Insulin-stimulated phosphorylation of CLASP2 by ERK regulates microtubule plus-end binding of CLASP2 and insulin-regulated microtubule stabilization.","authors":"James Krantz, DeHaven McCrary, Natalie K Barker, Sara S Parker, April Mengos, Mackenzie Roman, Skylar R Batty, Atley P Moberly, Corbin Jensen, Noel Warfel, Ghassan Mouneimne, Nam Y Lee, Lawrence J Mandarino, Paul R Langlais","doi":"10.1242/jcs.265004","DOIUrl":"https://doi.org/10.1242/jcs.265004","url":null,"abstract":"CLASP2, a microtubule plus-end tracking protein, exhibits changes in phosphorylation as well as localization along the microtubule in response to insulin stimulation. We report that CLASP2 is expressed in insulin target tissues such as skeletal muscle and adipose tissue and that CLASP2 protein abundance is decreased in epididymal fat of insulin resistant mice. Using a commercially available proline-directed phospho-antibody together with site-directed mutagenesis and quantitative proteomics, we establish that mouse CLASP2 (Uniprot ID Q8BRT1) undergoes insulin-stimulated phosphorylation at serines 884/893/1004/1005/1021 in 3T3-L1 adipocytes. Treatment of cells with the ERK inhibitor PD98059 inhibits the insulin-stimulated phosphorylation of CLASP2 at the proline-directed serines 893/1004/1005/1021. In vitro incubation of CLASP2 with ERK2 increases CLASP2 phosphorylation, whereas phosphorylation of a Ser884/893/1004/1005/1021Ala CLASP2 penta-mutant is decreased, indicating ERK2 is capable of directly phosphorylating CLASP2. When expressed in 3T3-L1 adipocytes, the CLASP2 penta-mutant presents significantly diminished insulin-stimulated microtubule plus-end trailing versus wildtype CLASP2. The lack of proline-directed, insulin-stimulated CLASP2 phosphorylation results in reduced insulin-induced microtubule stabilization. We introduce insulin-stimulated, proline-directed CLASP2 phosphorylation under control of the ERK pathway as a contributing factor for insulin-induced microtubule stabilization.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127589","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

Average local nucleosome motion remains nearly constant during interphase in living human cells. 在活的人类细胞间期，核小体的平均局部运动几乎保持不变。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265367

Yu Nagata, Shiori Iida, Masa A Shimazoe, Sachiko Tamura, Kako Nakazato, Kai Shimizu, Yuki Hatoyama, Masato T Kanemaki, Kazuhiro Maeshima

{"title":"Average local nucleosome motion remains nearly constant during interphase in living human cells.","authors":"Yu Nagata, Shiori Iida, Masa A Shimazoe, Sachiko Tamura, Kako Nakazato, Kai Shimizu, Yuki Hatoyama, Masato T Kanemaki, Kazuhiro Maeshima","doi":"10.1242/jcs.265367","DOIUrl":"https://doi.org/10.1242/jcs.265367","url":null,"abstract":"Dynamic chromatin behavior, which is related to chromatin accessibility, plays a critical role in various genome functions such as RNA transcription and DNA replication/repair. Previous studies using highly synchronized cells showed that average local chromatin motion, captured by single-nucleosome imaging on a subsecond time scale, remained nearly constant throughout G1, S, and G2 phases in living human cells. Here, we combined single-nucleosome imaging with Fucci cell-cycle probes to test this finding in asynchronous living human cells. Using HeLa and HCT116 cells expressing H2B-HaloTag and Fucci probes, we found that local nucleosome motion remained similar on average throughout interphase. Consistently, H3.3-Halo-labeled nucleosomes, which are enriched in Hi-C A compartments (euchromatin), also showed near-constant motion throughout interphase. Transcription inhibition increased nucleosome motion throughout interphase. Local nucleosome motion also increased following cellular perturbations, such as replication stress or DNA damage. Our findings suggest that near-constant chromatin motion supports housekeeping functions under similar physical conditions during interphase. They also suggest that cells can transiently change chromatin motion to perform ad hoc tasks in response to intra- and extracellular signals, such as DNA damage.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127621","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 truncated form of the cGMP-gated cation channel β-subunit lacking the GARP2 region transiently restores rod structure and function. 缺少GARP2区域的cgmp门控阳离子通道β-亚基的截断形式暂时恢复杆的结构和功能。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265168

Marci L DeRamus, Zhixian Zhang, Feng He, Alex S McKeown, Jeffrey D Messinger, Timothy W Kraft, Theodore G Wensel, Steven J Pittler

{"title":"A truncated form of the cGMP-gated cation channel β-subunit lacking the GARP2 region transiently restores rod structure and function.","authors":"Marci L DeRamus, Zhixian Zhang, Feng He, Alex S McKeown, Jeffrey D Messinger, Timothy W Kraft, Theodore G Wensel, Steven J Pittler","doi":"10.1242/jcs.265168","DOIUrl":"https://doi.org/10.1242/jcs.265168","url":null,"abstract":"The cGMP-gated channel β-subunit is required for phototransduction, disc morphogenesis, and structural integrity of rod cells. Its structural role may be mediated by its GARP2 (glutamic acid rich protein) domain. To assess domain functions, we generated transgenic mice expressing a truncated protein lacking the N-terminal region on a Cngb1 null background. In these mice, light microscopy showed normal disk morphology up to 6 months, and cryo-electron tomography revealed disc-to-plasma membrane connections similar to WT. However, the truncated protein was insufficient to prevent progressive degeneration leading to photoreceptor loss by 12-14 months. Truncated protein expression levels resembled WT β-subunit levels. The truncated protein localized both to the outer segment, like WT, but also elsewhere in rods. Electroretinography showed CNG channel function was comparable to WT at 1-month and remained so up to 7.5 months postnatal when marked declines appeared. Thus, the N-terminal extension of the β-subunit is required for long-term maintenance and survival of rod photoreceptors, whereas the major structural defects observed at early ages in the knockouts cannot be attributed to loss of the CNGB1a GARP2 domain or the GARP1 and GARP2 soluble proteins.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127602","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

CelFDrive: Multimodal deep learning-assisted microscopy for automated detection of rare events. CelFDrive：用于罕见事件自动检测的多模态深度学习辅助显微镜。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-06 DOI: 10.1242/jcs.265029

Scott Brooks, Sara Toral-Pérez, Nina Pučeková, David S Corcoran, Karl Kilborn, Brian Bodensteiner, Hella Baumann, Nigel J Burroughs, Andrew D McAinsh, Till Bretschneider

{"title":"CelFDrive: Multimodal deep learning-assisted microscopy for automated detection of rare events.","authors":"Scott Brooks, Sara Toral-Pérez, Nina Pučeková, David S Corcoran, Karl Kilborn, Brian Bodensteiner, Hella Baumann, Nigel J Burroughs, Andrew D McAinsh, Till Bretschneider","doi":"10.1242/jcs.265029","DOIUrl":"https://doi.org/10.1242/jcs.265029","url":null,"abstract":"The emergence of automated microscopy has enabled the collection of large datasets of rare biological events, accelerating discovery in biology. However, most existing methods cannot be readily integrated into microscopy set-ups or are limited to a single microscope type. We present CelFDrive, a software package that automatically detects rare events of interest and automates high-resolution 3D imaging of target cells by integrating deep-learning cell classification of auxiliary low-magnification fluorescence images. We show that CelFDrive reduced the mean time required to nominate a mitotic prophase candidate for high-resolution light-sheet imaging by over 30-fold relative to manual expert selection. This approach can be used to define the order of kinetochore assembly upon nuclear envelope breakdown. The trained CelFDrive detector demonstrated transferability by retaining mitotic-cell detection capability in an independently generated dataset using a different cell line, DNA marker and imaging setup. As datasets grow and models improve, CelFDrive offers a clear path toward intelligent imaging systems that not only accelerate data collection but also fundamentally enhance how biological questions are explored.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110236","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