Cytoskeleton (Hoboken, N.J.)最新文献

Harnessing Structure Prediction of Polo-Like Kinase 4 for Drug Repurposing.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-20 DOI: 10.1002/cm.22020

Harshita Kasera, Priyanka Singh

引用次数: 0

Introducing Our Associate Editorial Board Members: An Interview With Shu Yao Leong.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-18 DOI: 10.1002/cm.21951

Paul Trevorrow, Shu Yao Leong

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The Sole Essential Low Molecular Weight Tropomyosin Isoform of Caenorhabditis elegans Is Essential for Pharyngeal Muscle Function.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-13 DOI: 10.1002/cm.22014

Michael J Kimmich, Meaghan A Geary, Lei Mi-Mi, SarahBeth D Votra, Christopher D Pellenz, Sumana Sundaramurthy, David Pruyne

{"title":"The Sole Essential Low Molecular Weight Tropomyosin Isoform of Caenorhabditis elegans Is Essential for Pharyngeal Muscle Function.","authors":"Michael J Kimmich, Meaghan A Geary, Lei Mi-Mi, SarahBeth D Votra, Christopher D Pellenz, Sumana Sundaramurthy, David Pruyne","doi":"10.1002/cm.22014","DOIUrl":"10.1002/cm.22014","url":null,"abstract":"Tropomyosin is an actin-binding protein that plays roles ranging from regulating muscle contraction to controlling cytokinesis and cell migration. The simple nematode Caenorhabditis elegans provides a useful model for studying the core functions of tropomyosin in an animal, having a relatively simple anatomy and a single tropomyosin gene, lev-11, that produces seven isoforms. Three higher molecular weight isoforms regulate the contraction of body wall and other muscles, but comparatively less is known of the functions of four lower molecular weight isoforms (LEV-11C, E, T, U). We demonstrate here that C. elegans can survive with a single low molecular weight isoform, LEV-11E. Mutants disrupted for LEV-11E die as young larvae, whereas mutants lacking all other short isoforms are viable, with no overt phenotype. Vertebrate low molecular weight tropomyosins are often considered \"nonmuscle\" isoforms, but we find LEV-11E localizes to sarcomeric thin filaments in pharyngeal muscle and co-precipitates from worm extracts with the formin FHOD-1, which is also associated with thin filaments in pharyngeal muscle. Pharyngeal sarcomere organization is grossly normal in larvae lacking LEV-11E, indicating that the tropomyosin is not required to stabilize thin filaments, but pharyngeal pumping is absent, suggesting LEV-11E regulates actomyosin activity similar to higher molecular weight sarcomeric tropomyosin isoforms.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617871","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}

引用次数: 0

The PP2A-B56 Binding Site LxxIxE Contributes to Asp-Mediated Spindle Pole Stability.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-12 DOI: 10.1002/cm.22013

Margaux Quiniou, Maria C Burns, Aynsley McDermott, Karolina Jaworek, Stacey J Scott, James G Wakefield, Lori Borgal

{"title":"The PP2A-B56 Binding Site LxxIxE Contributes to Asp-Mediated Spindle Pole Stability.","authors":"Margaux Quiniou, Maria C Burns, Aynsley McDermott, Karolina Jaworek, Stacey J Scott, James G Wakefield, Lori Borgal","doi":"10.1002/cm.22013","DOIUrl":"https://doi.org/10.1002/cm.22013","url":null,"abstract":"The organization of microtubules into a mitotic spindle is critical for animal cell proliferation and involves the cooperation of hundreds of proteins whose molecular roles and regulation are not fully understood. The protein product of the Drosophila gene abnormal spindle, Asp, is a microtubule-associated protein required for correct mitotic spindle formation. To better understand the contribution of Asp to microtubule organization during spindle formation, we reverse-engineered flies to express a version of Asp (AspLIE), predicted to have lost its ability to bind the phosphatase trimer PP2A-B56. We demonstrated that the AspLIE mutation reduced an interaction with the Drosophila PP2A-B56 regulatory subunit Widerborst (Wdb), as well as other proteins with known roles in spindle formation. AspLIE flies exhibited less robust microtubule minus-end cohesion at neural stem cell spindle poles, which was accompanied by a substantial developmental delay but no microcephaly. Predictive structural modeling suggests that the presence of Wdb alters the conformation of an Asp interaction with a tubulin dimer in a manner similar to that of the AspLIE mutation. Protein localization in the Drosophila embryo, in addition to in vitro microtubule organization experiments, suggests that a role of PP2A may be to prevent Asp from contributing to microtubule cross-linking at spindle microtubule plus ends. Together, these findings add new insights to mechanisms underlying microtubule organization within the mitotic spindle.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607447","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}

引用次数: 0

Phosphorylation at the Helm: Kinase-Mediated Regulation of Primary Cilia Assembly and Disassembly.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-10 DOI: 10.1002/cm.22012

Andrea Lacigová, Lukáš Čajánek

引用次数: 0

The Interplay Between Early Chondrocyte Spreading and Inflammatory Responsivity.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-05 DOI: 10.1002/cm.22011

Tristan Isaiah Pepper, Saitheja Adi Pucha, Lauren Foster, Alan Y Liu, Meghan Alexander, Jay Milan Patel

{"title":"The Interplay Between Early Chondrocyte Spreading and Inflammatory Responsivity.","authors":"Tristan Isaiah Pepper, Saitheja Adi Pucha, Lauren Foster, Alan Y Liu, Meghan Alexander, Jay Milan Patel","doi":"10.1002/cm.22011","DOIUrl":"https://doi.org/10.1002/cm.22011","url":null,"abstract":"Joint injuries are increasingly common and initiate a degenerative cascade in the cartilage extracellular matrix. Chondrocytes experience both intra- and extra-cellular changes during the initial phases of this process, including inflammatory activation and morphological change, initiating a catabolic feedback cycle that progresses toward osteoarthritis (OA). However, the link between this early morphological spreading and susceptibility to future inflammatory events is unclear. Thus, the objective of this study was to explore the implications of cellular spreading on early inflammatory activation. First, we treated bovine cartilage explants with control or degenerative media for 2 weeks and established early chondrocyte spreading and extracellular matrix loss around chondrocytes. Next, we either seeded chondrocytes on or encapsulated them within gelatin hydrogels of different stiffnesses to allow different degrees of spreading, followed by a short (2 h) inflammatory stimulus to measure inflammatory activation (NF-κB). We found in 2D that stiffer substrates led to greater chondrocyte spreading and NF-κB nuclear localization; however, in 3D, this trend was reversed, with the greatest spreading and activation in cells in the softest hydrogels. Finally, we investigated how hyaluronic acid hydrogel incorporation into these environments could impact this spreading-inflammtory activation relationship, showing that augmentation with HA reduced both facets. In conclusion, chondrocyte spreading, especially in 3D, is linked with reduced matrix stiffness, and this can make chondrocytes more susceptible to inflammation. Thus, future therapies should seek to address not only the inflammation in the joint but also to restore chondrocyte morphology and microenvironmental properties.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560264","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}

引用次数: 0

The Microtubule Cytoskeleton in Bryophytes.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-05 DOI: 10.1002/cm.22009

Zihan Yin, Yirong Gan, Yin Chen, Elena Kozgunova, Peishan Yi

{"title":"The Microtubule Cytoskeleton in Bryophytes.","authors":"Zihan Yin, Yirong Gan, Yin Chen, Elena Kozgunova, Peishan Yi","doi":"10.1002/cm.22009","DOIUrl":"https://doi.org/10.1002/cm.22009","url":null,"abstract":"Microtubules (MTs) are essential cytoskeletal elements in all eukaryotes, playing critical roles in cell shape, intercellular organization, cell division, and cell motility. The organization of the MT network has undergone significant changes throughout plant evolution. Some MT structures, such as the preprophase band and phragmoplast, are innovations in plant lineages, while others, including the centriole and flagellum, have been lost over time. Bryophytes, consisting of mosses, liverworts, and hornworts, are the earliest land plants and occupy a key phylogenetic position in the evolution of MT organization. In the past two decades, advances in genomics, genetics, and cell imaging technologies have significantly enhanced our understanding of MT organization and function. Two representative species, Physcomitrium patens (moss) and Marchantia polymorph (liverwort), have become established model organisms, and new models for hornworts are emerging. In this review, we summarize the current knowledge of the MT cytoskeleton, drawing from early electron microscopy studies and recent advances in these emerging models. Our aim is to provide a comprehensive overview of the major MT array types and key factors involved in MT organization in bryophytes, offering insights into MT adaptation during plant evolution.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560265","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}

引用次数: 0

Fast Actin Disassembly and Fimbrin Mechanosensitivity Support Rapid Turnover in a Model of Clathrin-Mediated Endocytosis.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-03-04 DOI: 10.1002/cm.22002

Sayed Iman Mousavi, Michael M Lacy, Xiaobai Li, Julien Berro

{"title":"Fast Actin Disassembly and Fimbrin Mechanosensitivity Support Rapid Turnover in a Model of Clathrin-Mediated Endocytosis.","authors":"Sayed Iman Mousavi, Michael M Lacy, Xiaobai Li, Julien Berro","doi":"10.1002/cm.22002","DOIUrl":"https://doi.org/10.1002/cm.22002","url":null,"abstract":"The actin cytoskeleton is central to force production in numerous cellular processes in eukaryotic cells. During clathrin-mediated endocytosis (CME), a dynamic actin meshwork is required to deform the membrane against high membrane tension or turgor pressure. Previous experimental work from our lab showed that several endocytic proteins, including actin and actin-interacting proteins, turn over several times during the formation of a vesicle during CME in yeast, and their dwell time distributions were reminiscent of gamma distributions with a peak around 1 s. However, the distribution for the filament cross-linking protein fimbrin contains a second peak around 0.5 s. To better understand the nature of these dwell time distributions, we developed a stochastic model for the dynamics of actin and its binding partners. Our model demonstrates that very fast actin filament disassembly is necessary to reproduce experimental dwell time distributions. Our model also predicts that actin-binding proteins bind rapidly to nascent filaments and filaments are fully decorated. Last, our model predicts that fimbrin detachment from actin endocytic structures is mechanosensitive to explain the extra peak observed in the dwell time distribution.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544796","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}

引用次数: 0

Actin Filament Pointed Ends: Assays for Regulation of Assembly and Disassembly by Tropomodulin and Tropomyosin.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-02-24 DOI: 10.1002/cm.22007

Sawako Yamashiro, Shashank Shekhar, Stefanie M Novak, Sudipta Biswas, Carol C Gregorio, Velia M Fowler

{"title":"Actin Filament Pointed Ends: Assays for Regulation of Assembly and Disassembly by Tropomodulin and Tropomyosin.","authors":"Sawako Yamashiro, Shashank Shekhar, Stefanie M Novak, Sudipta Biswas, Carol C Gregorio, Velia M Fowler","doi":"10.1002/cm.22007","DOIUrl":"https://doi.org/10.1002/cm.22007","url":null,"abstract":"Actin filaments are dynamic polymers whose length depends on regulated monomer association and dissociation at their ends. Actin barbed-end dynamics are relatively better understood, primarily due to the approximately tenfold faster subunit on/off rates at barbed versus pointed ends. We present experimental approaches to selectively assay actin pointed-end regulation using bulk biochemistry, single filament imaging, and live cell microscopy with an emphasis on tropomodulins (Tmods), a conserved family of eukaryotic proteins that specifically cap pointed ends. Average pointed-end assembly/disassembly rates are measured in bulk solution using pyrene-labeled actin and barbed end-capping protein CapZ. Direct rate measurements of individual pointed ends are performed via microfluidic-assisted total internal reflection fluorescence microscopy (mf-TIRF). Actin pointed-end dynamics in living cells are examined in striated muscle cells expressing fluorescent actin, where the regular arrays of 1- to 2-μm-long actin filaments in sarcomeres enable visualization of filament pointed and barbed ends. These assays will also help advance our understanding of other pointed end regulators, including cyclase-associated protein and leiomodins, which have been implicated in filament stabilization, disassembly, and elongation. This work is relevant to the musculoskeletal field, where precise regulation of filament lengths is particularly critical for sarcomere organization and striated muscle contraction.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484800","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}

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Pharmacological Inhibition of β Myosin II Disrupts Sarcomere Assembly in Human iPSC-Derived Cardiac Myocytes.

Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-02-17 DOI: 10.1002/cm.22006

James B Hayes, Dylan T Burnette

{"title":"Pharmacological Inhibition of β Myosin II Disrupts Sarcomere Assembly in Human iPSC-Derived Cardiac Myocytes.","authors":"James B Hayes, Dylan T Burnette","doi":"10.1002/cm.22006","DOIUrl":"https://doi.org/10.1002/cm.22006","url":null,"abstract":"Sarcomeres are the fundamental contractile units of striated muscle. The functional roles of the cardiac-specific myosin heavy chains, MYH6 (α myosin II) and MYH7 (β myosin II) during sarcomere assembly remain controversial. To address this, we utilized a selective MYH7 inhibitor, mavacamten, in combination with siRNA-mediated knockdown of MYH6 or MYH7 in human induced pluripotent stem cell-derived cardiomyocytes (hiCMs). Our results demonstrate that sarcomere assembly proceeds when either MYH6 or MYH7 is independently depleted, suggesting functional redundancy. However, pharmacological inhibition of MYH7 contractility by mavacamten disrupts sarcomere assembly in a concentration-dependent manner. Sensitivity to mavacamten correlated with the relative abundance of MYH6 and MYH7: sarcomere assembly by MYH7-enriched (i.e., MYH6-depleted) hiCMs was more sensitive to mavacamten (IC50 = 0.1 μM), while assembly by MYH6-enriched (i.e., MYH7-depleted) hiCMs was less sensitive (IC50 = 0.5 μM). These findings suggest that MYH7-mediated contractility is required for sarcomere assembly, but only when MYH7 is present within a cardiac myocyte. We conclude that the MYH7/MYH6 ratio impacts the susceptibility of sarcomere assembly to pharmacological inhibition.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442841","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}

引用次数: 0