Cytoskeleton (Hoboken, N.J.)最新文献

{"title":"Author Profile (Trainee)-Shivani Tuli.","authors":"Shivani Tuli","doi":"10.1002/cm.70134","DOIUrl":"10.1002/cm.70134","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"213-214"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Septin Modifiers, Forchlorfenuron and UR214-9, on Mitochondrial Fragmentation and Lytic Cell Death.","authors":"Dominik Brokatzky, Rajdeep Das, Hannah Painter, Rakesh K Singh, Serge Mostowy","doi":"10.1002/cm.70013","DOIUrl":"10.1002/cm.70013","url":null,"abstract":"<p><p>Septins are conserved GTP-binding proteins that play key roles in cell division, mitochondrial dynamics and immune responses. Despite their importance to human health, pharmacological compounds to modify septins remain limited. Forchlorfenuron (FCF) was the first small molecule identified to modify septins, disrupting their organisation and promoting mitochondrial fragmentation. A more potent FCF analog (UR214-9) has recently been developed, but its effects on mitochondria were unknown. Here, we compare FCF and UR214-9 in vitro using macrophages and in vivo using zebrafish larvae. We demonstrate that both modifiers induce mitochondrial fragmentation in macrophages without altering mitochondrial mass or SEPT7 expression. Consistent with mitochondrial fragmentation, both modifiers trigger lytic cell death in a dose-dependent manner following lipopolysaccharide (LPS) priming. In vivo, both modifiers exhibit dose-dependent effects on the survival of zebrafish larvae, although UR214-9 was significantly more toxic. In agreement with in vitro results, we observed that FCF induces macrophage cell death and caspase-1 activity in zebrafish larvae. Together, our findings show that both septin modifiers impact mitochondrial integrity and macrophage survival. Understanding how septin modifiers regulate immune responses may have important implications for inflammatory disease research and could lead to the development of septin-based medicines for conditions characterised by dysregulated inflammation.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"179-186"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria and the Actin Cytoskeleton in Neurodegeneration.","authors":"Shivani Tuli, Preet Patel, Aneri Shethji, David Gau","doi":"10.1002/cm.70095","DOIUrl":"10.1002/cm.70095","url":null,"abstract":"<p><p>Mitochondrial dysfunction and cytoskeletal disorganization are widely recognized hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although these disorders differ in clinical presentation and etiology, accumulating evidence points to a shared cellular vulnerability at the intersection of mitochondrial dynamics and actin cytoskeletal regulation. In this review, we examine the emerging role of actin-mitochondria crosstalk as a convergent mechanism in neurodegeneration. We discuss how disruptions in actin filament remodeling, mitochondrial fission and fusion, organelle transport, and mitophagy contribute to neuronal dysfunction and loss across these diseases. Particular attention is given to disease-specific pathways, including cofilin-actin rod formation in AD, α-synuclein-driven actin disruption in PD, mutant huntingtin's effects on mitochondrial fragmentation in HD, and profilin-1-associated mitochondrial defects in ALS. By synthesizing findings from diverse models, we highlight how perturbations in the cytoskeleton-mitochondria interface may act as an upstream trigger and amplifier of neurodegenerative cascades. We also outline key knowledge gaps and propose future directions for research, with an emphasis on targeting actin-mitochondrial interactions as a potential therapeutic strategy across multiple neurodegenerative conditions.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"200-210"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talin1 Adhesion Morphology and Colocalization With Tensin3 Are Largely Unaffected by Polyacrylamide Substrate Stiffness.","authors":"Joanna Hajduk, Patrycja Twardawa, Sylwia Bobis-Wozowicz, Marta Szewczyk, Zenon Rajfur, Zbigniew Baster","doi":"10.1002/cm.70132","DOIUrl":"https://doi.org/10.1002/cm.70132","url":null,"abstract":"<p><p>Cells sense the stiffness of their extracellular matrix (ECM) and adapt their behavior accordingly. We investigated how ECM stiffness affects the spatial organization of talin1, a key mechanosensitive focal adhesion protein. Using polyacrylamide (PA) hydrogels with tunable stiffnesses (0.2-188 kPa), we analyzed cell morphology, migration, talin1 distribution, colocalization with tensin3, and fibronectin deposition. Softer substrates enhanced filopodia activity and altered migration behavior. On softer ECMs, talin1 exhibited a more uniform intracellular distribution. Conversely, on stiffer matrices, it was localized more towards the cell periphery. PA gels supported elongated talin1-based adhesions, whose morphology showed minimal variation across the 3-188 kPa stiffness range. Talin1-tensin3 colocalization was unaffected by PA gel stiffness, indicating a stable interaction. Notably, cells deposited more fibronectin on softer substrates. While talin1 adhesion morphology varied little with stiffness, cell migration behavior changed markedly. Combined with prior studies, our data suggest that ECM stiffness regulates talin1 primarily through conformational changes rather than remodeling of talin1 adhesion morphology. These findings highlight talin1's central role in translating mechanical cues into dynamic cellular responses.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"e70132"},"PeriodicalIF":1.6,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing Specific Tubulin Isotypes and Pathogenic Variants in Cellular Microtubule Arrays.","authors":"Sareen Fiaz, Benjamin Powers, Jayne Aiken","doi":"10.1002/cm.70127","DOIUrl":"https://doi.org/10.1002/cm.70127","url":null,"abstract":"<p><p>Eukaryotic cells depend on dynamic microtubule arrays to execute a wide range of functions vital for life. These microtubule filaments are formed through the polymerization of α/β-tubulin proteins, which can be generated from numerous tubulin genes, or isotypes. In the neuron, microtubule networks are responsible for a myriad of specialized functions, including neuronal migration, neurite extension, and long-range cargo transport. Pathogenic mutations in tubulin genes can result in a wide range of neurodevelopmental defects, collectively termed tubulinopathies. How distinct mutations within different tubulin genes lead to functional defects remains an area of active investigation. Neuronal microtubule networks are significantly challenging to visualize due to the dense, spatially confined microenvironments within the neuron. Further, the conserved nature of tubulin proteins makes the development of isotype-specific antibodies challenging. These factors pose a critical limitation to tubulinopathy research, making visualization of specific tubulin isotypes or mutant tubulin proteins inherently difficult. To address the current technological limitations, we describe a method for immunocytochemical labeling of a single ɑ-tubulin isotype harboring distinct pathogenic mutations. This approach utilizes a novel method for cellular tubulin visualization by inserting a hexahistidine (His6) epitope into a previously identified internal loop in the ɑ-tubulin protein. This modification acts as a visualization handle, providing direct evidence of the incorporation of ectopically expressed α-tubulin TUBA1A proteins into the cellular microtubule network using available 6×-His antibodies without disrupting tubulin function. We validate and describe this approach in human iNeurons and COS-7 cells-large, flat, fibroblast-like primate cells ideal for visualizing microtubule networks. This protocol highlights the efficacy of the His6-tag in wild-type TUBA1A, polymerization-defective mutant TUBA1A-N102D, and a highly polymer-stable mutant TUBA1A-E254A. This methodological pipeline can be harnessed to study the molecular and cellular phenotypes of numerous tubulin isotypes and pathogenic mutations.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"e70127"},"PeriodicalIF":1.6,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Distinct Molecular Features of FLNC Mutations, Associated With Different Clinical Phenotypes.","authors":"","doi":"10.1002/cm.70130","DOIUrl":"10.1002/cm.70130","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double Sided Traction Force Microscopy: A Method to Confine Cells for Physiologically Relevant Force Measurements.","authors":"Alexia Caillier, Patrick W Oakes","doi":"10.1002/cm.70129","DOIUrl":"10.1002/cm.70129","url":null,"abstract":"<p><p>In this paper we describe a technique to make a confined environment of variable stiffness that is suitable for high-resolution live-cell imaging. This versatile and adaptable technique enables cell confinement between soft elastic surfaces made from polyacrylamide gels. The two surfaces retain all their compatibility with multiple approaches to chemically couple adhesion proteins, and additional techniques like micropatterning and traction force microscopy. This method is thus well suited for measuring force production and migration of weakly adherent cells that struggle to migrate in traditional planar environments.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"e70129"},"PeriodicalIF":1.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidelines for Successful Actin Polymerization Experiments.","authors":"Thomas D Pollard","doi":"10.1002/cm.70115","DOIUrl":"https://doi.org/10.1002/cm.70115","url":null,"abstract":"<p><p>This perspective summarizes what has been learned about how to do actin filament polymerization experiments that produce data suitable for quantitative analysis.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147476535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking Mitotic Spindle Dynamics and Protein Localization in Fission Yeast With FYSKA, the Fission Yeast Spindle Kymograph Analyzer.","authors":"Bojun Zhou, Zachary R Gergely, Michele H Jones, Meredith D Betterton","doi":"10.1002/cm.70109","DOIUrl":"https://doi.org/10.1002/cm.70109","url":null,"abstract":"<p><p>Quantitative analysis of mitotic spindle dynamics requires accurate tracking despite challenges such as cell drift, spindle rotation, and fluctuating fluorescence signals. We developed the Fission Yeast Spindle Kymograph Analyzer (FYSKA), an automated software tool that tracks the spindle and constructs kymographs of spindle-associated proteins in Schizosaccharomyces pombe. FYSKA uses fluorescent spindle pole markers to achieve sub-pixel precision, applies error correction for transient signal loss, and maintains robustness under rotation or drift. Compared to semi-automated approaches, it generates kymographs with more consistent intensity profiles and improved capture of the spindle axis. Using FYSKA, we quantified spindle length fluctuations and examined localization patterns of the kinesin-5 motor Cut7 including asymmetric spindle pole recruitment in Cut11-7. These examples show how FYSKA enables automated, reproducible analysis of mitotic spindle organization and protein dynamics.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arp2/3 Inhibition Suppresses Membrane Dynamics but Does Not Block Pigment Granule Migration in Isolated Fish Retinal Pigment Epithelial (RPE) Cells.","authors":"Keelan O'Reilly, Taiki Tashiro, Kristina Kristo, Christina King-Smith","doi":"10.1002/cm.70128","DOIUrl":"https://doi.org/10.1002/cm.70128","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) lies at the back of the vertebrate eye and plays important roles in vision. In the eyes of fish, which lack dilatable pupils, RPE pigment granules undergo massive migrations to regulate light intensity. Previous work has demonstrated that both aggregation and dispersion of pigment granules through apical projections of RPE require an intact actin cytoskeleton. To determine the role of the actin-nucleating complex, Arp2/3, on pigment granule movement, isolated RPE cells were treated with the inhibitors CK-666 and CK-869. Both drugs caused a reversible rapid cessation of both lateral and distal membrane extension of the cells' apical projections, resulting in an overall thinning of the projections. CK-666 also stimulated the formation of F-actin aggregates in projections, mainly at the distal tips. Despite these structural changes, these inhibitors had no effect on pigment granule aggregation or dispersion. Immunolocalization of Arp3 showed diffuse fluorescence throughout isolated cells. The actin side-binding protein, tropomyosin, was also present in RPE cells, aligning with F-actin bundles. While it cannot be ruled out that these drugs only partially inhibited Arp2/3 complex nucleation, the results suggest that while actin nucleation by Arp2/3 inhibition is important in membrane dynamics of the RPE apical projections, it is not critical for pigment granule movement.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"e70128"},"PeriodicalIF":1.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}