Journal of cell science最新文献_第5页

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

CRB3 and ARP2/3 regulate cell biomechanical properties to set epithelial monolayers for collective movement. CRB3和ARP2/3调节细胞的生物力学特性，设置上皮单分子层进行集体运动。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-06 DOI: 10.1242/jcs.263667

Dominique Massey-Harroche, Vito Conte, Niels Gouirand, Juna Como, Michäel Sebbagh, André Le Bivic, Elsa Bazellières

{"title":"CRB3 and ARP2/3 regulate cell biomechanical properties to set epithelial monolayers for collective movement.","authors":"Dominique Massey-Harroche, Vito Conte, Niels Gouirand, Juna Como, Michäel Sebbagh, André Le Bivic, Elsa Bazellières","doi":"10.1242/jcs.263667","DOIUrl":"https://doi.org/10.1242/jcs.263667","url":null,"abstract":"Several cellular processes during morphogenesis, tissue healing or cancer progression involve collective cell migration. To set the cells for motion, there is an initial breaking of organization of the epithelial tissue that modifies the epithelial phenotype and axis of polarity. During this process, the actin cytoskeleton and cellular junctions are extensively remodeled correlating with the buildup of mechanical forces. As the collective migration proceeds, mechanical forces generated by the actin cytoskeleton align with the direction of migration ensuring an organized and efficient collective cell behavior, but how forces are regulated during the breaking of symmetry at the onset of collective motion remains an unaddressed question. It is known that the polarity complex CRB3/PALS1/PATJ, and in particular, CRB3 regulates the organization of the actin cytoskeleton associated to the apical domain thus pointing at a potential role of CRB3 in controlling mechanical forces. Whether and how CRB3 influences epithelial biomechanics during collective cell motion remains, however, largely unexplored. Here, we systematically combine mechanical and molecular analyses to show that CRB3 regulates the biomechanical properties of collective epithelial cells during the initial breaking of epithelial tissue organization. CRB3 interacts with ARP2/3 and controls the remodeling of actin via the modulation of the Rho-/Rac-GTPase balance, and more precisely by acting upstream of the activation of Rac1. Taken together, our results identified CRB3, a polarity protein, as a regulator of epithelial monolayer mechanics during collective cell motion.","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":"149110270","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

Tubulin polyglutamylation modulates Golgi morphodynamics and neurite branching during neuronal morphogenesis. 小管蛋白多谷氨酰化在神经元形态发生过程中调节高尔基体形态动力学和神经突分支。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-02 DOI: 10.1242/jcs.264960

Chih-Hsuan Hsu, Alexander Josiah Kinrade, Sarah Cohen

{"title":"Tubulin polyglutamylation modulates Golgi morphodynamics and neurite branching during neuronal morphogenesis.","authors":"Chih-Hsuan Hsu, Alexander Josiah Kinrade, Sarah Cohen","doi":"10.1242/jcs.264960","DOIUrl":"https://doi.org/10.1242/jcs.264960","url":null,"abstract":"Neurons establish functional networks through morphological remodeling during neuronal differentiation. Microtubule polyglutamylation is a key microtubule post-translational modification that is highly enriched during this process and plays an important role in differentiation. However, how remodeling of organelle features such as morphology, distribution and interactions depends on tubulin polyglutamylation during neuronal differentiation remain unclear. Here, we employed multispectral imaging combined with quantitative 3D organelle analysis to comprehensively profile eight organelles simultaneously in human induced pluripotent stem cell-derived neurons. We discovered that depletion of tubulin polyglutamylation induces pronounced alterations in somatic Golgi morphology and associated organelle interactions. In addition, Golgi-derived compartments in proximal neurites exhibited altered morphology and dynamics, namely decreased anterograde transport together with less efficient movement. These changes were accompanied by increased neurite branching and tortuosity. Together, our findings reveal a previously unrecognized role for tubulin polyglutamylation in coordinating organelle organization with neurite architecture, providing a mechanistic link between tubulin post-translational modification, Golgi morphology, dynamics, and neuronal morphogenesis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109823","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

Distinct roles for TANGO1S domains in maintaining ER-Golgi architecture. TANGO1S域在维护er -高尔基体系结构中的不同角色。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-02 DOI: 10.1242/jcs.265001

Elizabeth A Lawrence, Lorna Hodgson, Judith Mantell, M Esther Prada-Sanchez, Chrissy L Hammond, David J Stephens, Nicola L Stevenson

{"title":"Distinct roles for TANGO1S domains in maintaining ER-Golgi architecture.","authors":"Elizabeth A Lawrence, Lorna Hodgson, Judith Mantell, M Esther Prada-Sanchez, Chrissy L Hammond, David J Stephens, Nicola L Stevenson","doi":"10.1242/jcs.265001","DOIUrl":"https://doi.org/10.1242/jcs.265001","url":null,"abstract":"The endoplasmic reticulum (ER)-Golgi interface is a dynamic trafficking hub maintained in part by TANGO1, a scaffolding protein that coordinates proteins and membranes at ER exit sites (ERES). TANGO1 has two isoforms: TANGO1L, which has a lumenal SH3 domain, and TANGO1S, which lacks this domain but retains the transmembrane and cytoplasmic coiled-coil (CC), TEER, and PRD domains common to both forms. We showed previously that loss of both isoforms disrupts ER-Golgi organization more severely than TANGO1L loss alone, indicating TANGO1S is functional and can compensate. Here we dissect the role of each TANGO1 cytoplasmic domain in maintaining secretory pathway organisation by expressing TANGO1S domain-deletion mutants in TANGO1L-/S- knockout cells. We show that TANGO1 loss causes cis-Golgi vesiculation that cannot be rescued by TANGO1S. TANGO1S re-expression also failed to rescue COPII and Sec16 recruitment in this cell line. Meanwhile, the TEER domain is essential for the organisation of the ER, and the TEER, CC2 and PRD domain are required for a defined ERGIC. This study represents an advance towards a domain-level resolution of TANGO1S function.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110268","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

Understanding the unfolded protein response in glioblastoma. 了解胶质母细胞瘤中未折叠蛋白的反应。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-15 DOI: 10.1242/jcs.264879

Kaixiang Ni, Chenchen Shi, Jiantong Jiao, Jun Sun, Yan Chen, Yi Liu

{"title":"Understanding the unfolded protein response in glioblastoma.","authors":"Kaixiang Ni, Chenchen Shi, Jiantong Jiao, Jun Sun, Yan Chen, Yi Liu","doi":"10.1242/jcs.264879","DOIUrl":"https://doi.org/10.1242/jcs.264879","url":null,"abstract":"Glioblastoma is the most aggressive and lethal malignancy of the central nervous system and exhibits a complex interplay with endoplasmic reticulum (ER) stress (ERS). The multifunctional ER is the primary site of the unfolded protein response (UPR), which is activated under conditions of ERS to enhance protein-folding capacity and promote cell survival. However, persistent ERS can trigger apoptosis. Despite extensive research over the past decades, the mechanistic insights into the impact of ERS and the UPR on glioblastoma pathogenesis and progression remain unclear. The UPR operates through three canonical signaling pathways: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK, also known as EIF2AK3) and activating transcription factor 6 (ATF6). These pathways regulate glioblastoma development through both independent and synergistic mechanisms. In this Review, we discuss the current state of research on the role of the UPR in glioblastoma and delineate the distinct mechanisms of each signaling pathway. Furthermore, we evaluate the challenges associated with UPR-targeting therapeutic agents and propose possible treatment strategies to leverage the regulatory mechanisms of the different UPR pathways to overcome these limitations.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 19","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182098","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

Mechanotransduction through LFA-1 controls upstream migration in the KG-1a stem cell line. 通过LFA-1的机械转导控制KG-1a干细胞系的上游迁移。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-14 DOI: 10.1242/jcs.265036

Ai Mochida, Emily Valerio, Janis K Burkhardt, Daniel A Hammer

{"title":"Mechanotransduction through LFA-1 controls upstream migration in the KG-1a stem cell line.","authors":"Ai Mochida, Emily Valerio, Janis K Burkhardt, Daniel A Hammer","doi":"10.1242/jcs.265036","DOIUrl":"10.1242/jcs.265036","url":null,"abstract":"Immune cell recruitment into tissues requires cells to migrate on the endothelium while overcoming shear forces. Many extravasating cells, including T lymphocytes and hematopoietic stem cells, migrate upstream against the direction of shear flow on ICAM-1. Upstream migration has been shown to depend on intracellular signaling through Crk family adaptor proteins following engagement of lymphocyte function-associated antigen-1 (LFA-1). Because upstream migration is an important illustration of leukocyte mechanotransduction, we sought to identify key intracellular regulators of upstream migration using CRISPR/Cas9 gene editing and the KG-1a stem cell line. We made targeted deletions of molecules that function downstream of LFA-1 to regulate actin polymerization, link integrin signaling to the actin cytoskeleton, or form scaffolding complexes with Crk proteins. We found that CrkL, CasL (also known as HEF1 or NEDD9), L-plastin (LCP1) and RIAM (APBB1IP) are crucial for dynamic F-actin-rich lamellipodia and upstream migration. Although WASP (WAS), Hem1 (NCKAP1L), EVL and vinculin were found to be dispensable for upstream migration, pan-formin inhibition with SMIFH2 revealed a role for formins in upstream migration. This study illustrates the role of LFA-1 mechanotransduction in driving F-actin assembly at the leading edge to drive upstream migration.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 19","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182046","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

Responses to endoplasmic reticulum stress at a glance. 内质网应激反应一览。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-08 DOI: 10.1242/jcs.264817

Eric Chevet, Céline Philippe, Tony Avril, Elodie Lafont

{"title":"Responses to endoplasmic reticulum stress at a glance.","authors":"Eric Chevet, Céline Philippe, Tony Avril, Elodie Lafont","doi":"10.1242/jcs.264817","DOIUrl":"https://doi.org/10.1242/jcs.264817","url":null,"abstract":"The endoplasmic reticulum (ER) is the gateway to the eukaryotic protein secretory pathway. Beyond its role in protein biogenesis, it is central to Ca2+ homeostasis and lipid biosynthesis. This organelle, which can constitute more than 50% of the cellular membranes in secretory cells, is highly plastic and must adjust to intracellular or extracellular challenges to ensure proper protein secretion. ER stress, resulting from challenges such as accumulation, misfolding or aggregation of proteins or from disrupted ER lipid composition, can deleteriously affect cell function. Thus, the ER has evolved adaptive mechanisms that lead to cellular reprogramming to adjust its capacity to handle stress, including the unfolded protein response (UPR), which engages various ER quality control systems, protein degradation pathways and ER-organelle contacts. If this succeeds, the cell survives; but if it fails, cell death mechanisms are triggered. In this Cell Science at a Glance article and the accompanying poster, we summarize current knowledge on ER stress and control of the UPR in mammalian cells, highlighting aspects that require further attention. We also discuss recent insights that must be considered to better capture the full understanding of the ability of the ER to adjust to biological variation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 19","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136756","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

Msh2 depletion impairs cell differentiation, proliferation and metabolism in esophageal organoids. Msh2耗竭会损害食管类器官的细胞分化、增殖和代谢。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-19 DOI: 10.1242/jcs.264470

Marjorie Rolland, Dominique Jean, Maude Hamilton, Molly Sedeuil, Alexis Gonneaud, Line Berthiaume, Étienne Audet-Walsh, Véronique Giroux

{"title":"Msh2 depletion impairs cell differentiation, proliferation and metabolism in esophageal organoids.","authors":"Marjorie Rolland, Dominique Jean, Maude Hamilton, Molly Sedeuil, Alexis Gonneaud, Line Berthiaume, Étienne Audet-Walsh, Véronique Giroux","doi":"10.1242/jcs.264470","DOIUrl":"10.1242/jcs.264470","url":null,"abstract":"Given its rapid cell turnover, the esophageal stratified squamous epithelium must maintain homeostasis. This process is ensured by a long-lived subpopulation of basal stem cells that express keratin 15 (Krt15). However, the mechanisms that specifically control their characteristics, namely, self-renewal, multipotency and regeneration, remain unknown. Interestingly, MutS homolog 2 (Msh2), implicated in the DNA mismatch repair pathway, is the most upregulated gene in Krt15-positive esophageal stem cells compared to Krt15-negative cells. Accentuated DNA repair capacity is often observed in stem cells to maintain their genomic integrity and avoid the acquisition of mutations. Hence, this study aimed to evaluate the effects of Msh2 loss on stem cell functions, including differentiation, clonogenicity and proliferation, in murine esophageal organoids. Msh2-depleted organoids were generated by CRISPR/Cas9. They displayed morphogenic alterations and significant homeostasis perturbations. Cell differentiation was decreased while clonogenicity and proliferation were increased. Loss of Msh2 also caused lower expression of stem cell markers and changes in response to chemotherapy drugs. Proteomic analysis confirmed variations in epithelial cell differentiation and showed major changes in proteins associated with metabolic processes. In line with these results, metabolomic analysis confirmed an altered abundance of various metabolites of the tricarboxylic acid cycle and biosynthetic pathways. In conclusion, these results showed that Msh2 is implicated in the homeostasis of esophageal organoids, potentially through metabolic rewiring.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603364","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

Expression of Concern: Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation. 表达关注：胚胎干细胞聚集诱导Nanog抑制和原始内胚层分化。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-16 DOI: 10.1242/jcs.265375

Takashi Hamazaki, Masahiro Oka, Shinya Yamanaka, Naohiro Terada

引用次数: 0