Junya Hayase, Li Yang, Yu-Heng Zhou, Kangji Wang, Cheng-Ran Xu, Erfei Bi
{"title":"E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity.","authors":"Junya Hayase, Li Yang, Yu-Heng Zhou, Kangji Wang, Cheng-Ran Xu, Erfei Bi","doi":"10.1083/jcb.202509170","DOIUrl":"10.1083/jcb.202509170","url":null,"abstract":"<p><p>Hepatocytes display a unique polarity, forming narrow apical tubes-bile canaliculi (BCs)-between adjacent cells that are essential for liver function. Unlike most epithelial cells, hepatocytes express both E- and N-cadherin, yet their specific roles during BC tubulogenesis remain incompletely understood. Here, we show that these cadherins are collectively required for hepatic polarity and BC formation yet act through distinct mechanisms. E-cadherin localizes to adherens junctions, lateral membranes, and the cleavage furrow, where it promotes division-linked BC elongation and cell-cell contact formation by controlling spindle orientation and RhoA activation via NuMA and ARHGEF17. In contrast, N-cadherin is restricted to adherens junctions and maintains hepatic polarity by attenuating RhoA activity through the p120-catenin family member ARVCF and its partner p190B/ARHGAP5. Together, these findings reveal that dual cadherin expression drives hepatic polarity and BC formation by controlling RhoA activity in a coordinated yet opposing manner.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030865","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}
Erqing Gao, Liwei Guan, Kehang Zhang, Shuze Qi, Jingxiu Xu, Jie Zhang, Tianyi Zhu, Bing Yang, Chonglin Yang, Eric Miska, Mao Zhang, Suhong Xu
{"title":"A cytosolic IF1 reporter enables real-time visualization of severe mitochondrial membrane damage.","authors":"Erqing Gao, Liwei Guan, Kehang Zhang, Shuze Qi, Jingxiu Xu, Jie Zhang, Tianyi Zhu, Bing Yang, Chonglin Yang, Eric Miska, Mao Zhang, Suhong Xu","doi":"10.1083/jcb.202511088","DOIUrl":"10.1083/jcb.202511088","url":null,"abstract":"<p><p>Maintenance of mitochondrial integrity is fundamental for cellular survival, yet how cells recognize catastrophic mitochondrial membrane damage remains unknown. Here, we identify MAI-1 as the first genetically encoded reporter of severe mitochondrial membrane damage. MAI-1 is a Caenorhabditis elegans homolog of the ATP synthase inhibitor IF1 that lacks a mitochondrial targeting sequence, resides in the cytosol under basal conditions, but rapidly and irreversibly translocates to severely damaged mitochondria within milliseconds. We validate MAI-1 across diverse injury paradigms and demonstrate that cytosolic IF1 variants from other species exhibit conserved damage-induced recruitment. Mechanistically, MAI-1 recruitment requires the presence of an intact ATP synthase complex. Using MAI-1 as a sensor, we uncover that these severely damaged mitochondria are cleared through the LGG-1-mediated, PINK1/PARKIN-independent lysosomal pathway. Together, our findings establish a powerful tool for visualizing severe mitochondrial membrane damage and reveal a surveillance mechanism dedicated to structural integrity control.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143619","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}
Journal of Cell BiologyPub Date : 2026-08-03Epub Date: 2026-07-22DOI: 10.1083/jcb.20241020606232026c
Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek
{"title":"Correction: Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex.","authors":"Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek","doi":"10.1083/jcb.20241020606232026c","DOIUrl":"10.1083/jcb.20241020606232026c","url":null,"abstract":"","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549107","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}
{"title":"Tunneling nanotubes and cytonemes in cancer and development.","authors":"Kenneth M Yamada, David A Cruz Walma, Wakako Endo","doi":"10.1083/jcb.202601085","DOIUrl":"https://doi.org/10.1083/jcb.202601085","url":null,"abstract":"<p><p>Embryonic, adult, and cancer cells can exchange cytoplasmic proteins and even organelles using long, slender nanotubular interconnections. These cytoplasmic extensions, termed cytonemes, tunneling nanotubes, or tumor microtubes, span a spectrum of sizes. They have a structural core of F-actin filaments and can transport proteins and organelles ranging in size from small vesicles to mitochondria. These nanotubular interconnections can support embryonic development and tissue-tissue interactions as well as cancer cell defense against hypoxia, metabolic stressors, and chemotherapy. For example, tunneling nanotubes can transfer mitochondria to immune cells from non-malignant or tumor cells to promote or disable tumor cell killing. Numerous molecules initiate and maintain these nanotubular structures, suggesting cell type specificity. Many unanswered conceptual and mechanistic questions remain concerning the molecular and regulatory mechanisms driving their generation, structural and cell type-specific versus universal properties, and potential for novel therapeutic interventions-all providing exciting new opportunities in this rapidly expanding field of cell biology.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619951","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}
{"title":"Redox-dependent S-glutathionylation of Aurora-A kinase by Gstp promotes postsynaptic maturation.","authors":"Shuji Wakatsuki, Akiko Yumoto, Takehiro Suzuki, Naoshi Dohmae, Toshiyuki Araki","doi":"10.1083/jcb.202509200","DOIUrl":"10.1083/jcb.202509200","url":null,"abstract":"<p><p>Synapse formation relies on the precise orchestration of signaling pathways within postsynaptic compartments. Although we previously identified Aurora-A kinase as a promoter of synaptogenesis, the mechanism by which it is activated in postmitotic neurons lacking canonical cell cycle cofactors has remained elusive. Here, we identify a neuron-specific regulatory mechanism in which Pi-class glutathione S-transferase catalyzes S-glutathionylation of Aurora-A at C290 in response to localized redox fluctuations. This priming event catalytically promotes Aurora-A dimerization and subsequent autophosphorylation at T288, thereby enhancing kinase activity independently of classical mitotic activators. Activated Aurora-A then phosphorylates major vault protein at S563 and S585, destabilizing the vault complex and initiating local MEK/extracellular signal-regulated kinase signaling, which drives synaptogenesis. Together, these findings define a Gstp-Aurora-A-Mvp signaling axis that links localized redox dynamics to synaptic maturation and illustrates how neurons repurpose potent mitotic machinery through precise catalytic redox regulation, with significant implications for understanding kinase dysregulation in neurodevelopmental and neurodegenerative disorders associated with oxidative stress.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225348","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}
Soumya Bhattacharyya, Jose Wojnacki, Nathalie Brouwers, Vivek Malhotra
{"title":"Procollagen 1 assembles into phase-separated condensates in the endoplasmic reticulum.","authors":"Soumya Bhattacharyya, Jose Wojnacki, Nathalie Brouwers, Vivek Malhotra","doi":"10.1083/jcb.202603129","DOIUrl":"10.1083/jcb.202603129","url":null,"abstract":"<p><p>Procollagen I (PC1) is assembled into a trimer within the lumen of the endoplasmic reticulum (ER). In vitro, collagen trimers form rigid molecules reaching lengths of up to 400 nm, and this conformation is presumed to represent their assembled state in vivo. Here, we demonstrate that endogenous PC1 assembles into biomolecular condensates in the ER of activated human hepatic stellate cells. PC1 condensates form in response to increased collagen synthesis and are part of a multicomponent system enriched in the chaperones Hsp47 and calreticulin, as well as the disulfide isomerases PDIA1 and PDIA6, but notably lacking the unfolded protein sensor BiP. PC1 condensates localize to ER exit sites, a process mediated by TANGO1, and dissipate upon ER stress. We propose that this organization enables the accommodation of large quantities of PC1 in the ER lumen without triggering degradation. Furthermore, we suggest that PC1 within condensates is exported in a manner resembling liquid extrusion rather than as a rigid trimer.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217521","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}
Isabella M Gaeta, Shuangshuang Du, Clémentine Villeneuve, David G Gonzalez, Catherine Matte-Martone, Smirthy Ganesan, Deandra Simpson, Hilldana Tibebu, Jessica L Moore, Chen Yuan Kam, Sara Gallini, Haoyang Wei, Fabien Bertillot, Dagmar Zeuschner, Lauren E Gonzalez, Ushnish Rana, Kaelyn D Sumigray, Sara A Wickström, Valentina Greco
{"title":"Fibroblast depletion reveals mammalian epithelial resilience across neonatal and adult stages.","authors":"Isabella M Gaeta, Shuangshuang Du, Clémentine Villeneuve, David G Gonzalez, Catherine Matte-Martone, Smirthy Ganesan, Deandra Simpson, Hilldana Tibebu, Jessica L Moore, Chen Yuan Kam, Sara Gallini, Haoyang Wei, Fabien Bertillot, Dagmar Zeuschner, Lauren E Gonzalez, Ushnish Rana, Kaelyn D Sumigray, Sara A Wickström, Valentina Greco","doi":"10.1083/jcb.202507165","DOIUrl":"10.1083/jcb.202507165","url":null,"abstract":"<p><p>Regenerative organs, like the skin, depend on niche-stem cell interactions that sustain cellular turnover. In culture, skin fibroblasts promote epidermal stem cell proliferation and differentiation. Yet, it remains elusive how fibroblasts regulate epidermal stem cell behaviors and differentiation in vivo in skin. Here, we asked how fibroblast depletion may impact proliferation of the epidermal stem cell compartment. Surprisingly, we find that significant depletion of fibroblast density does not affect epidermal stem cell proliferation during adult or neonatal stages in vivo. These results demonstrate that across different ages, proliferation of epidermal stem cells can persist in the face of a depleted fibroblast population. Interestingly, neonatal fibroblast depletion does not significantly reduce collagen I density but affects basement membrane mechanics and epidermal stem cell delamination. Despite these changes, the skin continues to maintain its protective barrier function. Thus, our work demonstrates the skin regenerative program employs robust compensatory mechanisms in response to fibroblast depletion to maintain functional capacity.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225079","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}
Kaspar Gierke,Michalina Gadomska,Julia Breuer,Julius N Bahr,Tanja M Müller,Hanna Ehnis,Sina Zobel,Nancy Mejia Villagran,Sonja A Kirsch,Alexandra Skrzypek,Renato Frischknecht,Anna Fejtová,Rainer A Böckmann,Carolin Wichmann,Hanna Regus-Leidig,Johann Helmut Brandstätter
{"title":"The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons.","authors":"Kaspar Gierke,Michalina Gadomska,Julia Breuer,Julius N Bahr,Tanja M Müller,Hanna Ehnis,Sina Zobel,Nancy Mejia Villagran,Sonja A Kirsch,Alexandra Skrzypek,Renato Frischknecht,Anna Fejtová,Rainer A Böckmann,Carolin Wichmann,Hanna Regus-Leidig,Johann Helmut Brandstätter","doi":"10.1083/jcb.202509110","DOIUrl":"https://doi.org/10.1083/jcb.202509110","url":null,"abstract":"Retinal photoreceptors transmit light signals to their postsynaptic neurons with high precision, speed and without fatigue. This high-throughput neurotransmission relies on a sophisticated molecular machinery centered on a presynaptic organelle, the synaptic ribbon (SR). A hallmark of SRs is the recruitment of synaptic vesicles (SVs) from the cytoplasmic SV pool via \"tethering\". However, the identity of the tether and the mechanism underlying SV tethering are unknown. Here, we show that cell-specific deletion of the SR-associated protein Piccolino from rod photoreceptors disrupts SR morphology and ablates SV tethering. Nanoscale epitope mapping suggests that Piccolino acts as an SV tether by extending its N terminus away from the SR into the SV-filled terminal cytoplasm. With in silico modeling and protein lipid-binding assays, we demonstrate that an amphipathic liquid packing sensor motif (ALPS) at the N terminus of Piccolino binds SV-like liposomes, implicating this interaction as the mechanism underlying SV tethering. Together, our findings identified Piccolino as the molecular link between the SR and SVs.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552525","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}
Analeigha V Colarusso,Alison C E Wirshing,Daniel J Lew
{"title":"Septins and cytokinesis in the polymorphic fungus Aureobasidium pullulans.","authors":"Analeigha V Colarusso,Alison C E Wirshing,Daniel J Lew","doi":"10.1083/jcb.202601114","DOIUrl":"https://doi.org/10.1083/jcb.202601114","url":null,"abstract":"During cytokinesis of animal and fungal cells, a contractile actomyosin ring (CAR) assembles at target locations and constricts to drive cell separation. In animal cells, the position of the CAR is determined by the mitotic spindle so that the cleavage plane is perpendicular to the mitotic axis. However, in budding yeasts, the location of CAR assembly is specified by a cortical septin cytoskeleton that recruits CAR components to the neck. In the polymorphic fungus Aureobasidium pullulans, we show that septins assemble at mother-bud necks and predict the sites of CAR assembly. Cells lacking septins stochastically failed to assemble CARs at a subset of bud necks. However, even cells lacking all four core septins were able to assemble CARs at 75% of bud necks. Our findings suggest the existence of a novel pathway that enables CAR positioning, assembly, and constriction with no requirement for septin scaffolds or nuclear/spindle cues.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"10 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462468","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}
{"title":"Satellite view: Dissection of PCM1 assembly processes reveals centriolar satellite structures.","authors":"Ruth M Kearney,Anushka Sharma,Ciaran G Morrison","doi":"10.1083/jcb.202606168","DOIUrl":"https://doi.org/10.1083/jcb.202606168","url":null,"abstract":"Centriolar satellites (CS) are dynamic and heterogeneous granular assemblies that concentrate around centrosomes and contribute to ciliogenesis. In this issue, Begar et al. (https://doi.org/10.1083/jcb.202509238) examine the CS scaffold protein PCM1 to dissect CS assembly and structure during the cell cycle and ciliogenesis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"15 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462199","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}