Cytoskeleton最新文献

{"title":"Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma","authors":"Alexandra Pittar,&nbsp;Edward J. Buckley,&nbsp;Sarah T. Boyle,&nbsp;S. Jan Ibbetson,&nbsp;Michael S. Samuel","doi":"10.1002/cm.21894","DOIUrl":"10.1002/cm.21894","url":null,"abstract":"<p>A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression. RHO-ROCK signaling, and consequent tension within the cellular actomyosin cytoskeleton, regulates a paracrine signaling cascade that establishes a tumor-promoting microenvironment. Here, we show that consistent with our observations in breast cancer, enhanced ROCK activity and consequent production of CRELD2 is associated with the recruitment and tumor-promoting polarization of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. Our observations provide support for the notion that the role of RHO-ROCK signaling in establishing a tumor-promoting microenvironment may be conserved across patients and potentially also different cancer types.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"81 12","pages":"864-871"},"PeriodicalIF":2.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.21894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of actin-binding proteins in cataract formation","authors":"Christina Karakosta,&nbsp;Martina Samiotaki,&nbsp;George Panayotou,&nbsp;Dimitrios Papakonstantinou,&nbsp;Marilita M. Moschos","doi":"10.1002/cm.21889","DOIUrl":"10.1002/cm.21889","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Actin has been implicated in lens opacification; however, the specific actin-related pathways involved in cataracts remain unelucidated. In this study, actin-related proteome changes and signaling pathways involved in the development of cataracts were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from 11 patients with diabetic cataract (DC), 12 patients with age-related cataract (ARC), and seven patients with post-vitrectomy cataract (PVC). Untargeted, global identification and quantification of proteins was performed through liquid chromatography-mass spectrometry with the data-independent acquisition (DIA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In phaco cassette samples, proteins with significantly lower expression in ARC than in DC and PVC were involved in various pathways, including actin binding, actin cytoskeleton reorganization, actin filament capping, cortical actin cytoskeleton organization, and small GTPase-mediated signal transduction pathways. In anterior capsules, proteins with significantly lower expression in ARC than in DC and PVC were involved in actin binding and actin cytoskeleton reorganization pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Actin cytoskeleton and actin-binding proteins are involved in lens fiber elongation and differentiation. Rho GTPases contribute to actin cytoskeletal reorganization, and their inactivation is linked to abnormal lens fiber migration. These findings link actin binding to lens fiber integrity, lens opacification, and cataracts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 3","pages":"98-110"},"PeriodicalIF":2.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.21889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Axonemal tubules in the distal sperm tail of Wolbachia-infected Drosophila simulans males contain ring-like intraluminal structures that persist after axoneme fragmentation","authors":"Ambra Pratelli,&nbsp;Maria Giovanna Riparbelli,&nbsp;Giuliano Callaini","doi":"10.1002/cm.21891","DOIUrl":"10.1002/cm.21891","url":null,"abstract":"<p><i>Wolbachia</i> are obligate intracellular alphaproteobacteria that enhance their spreading by altering the reproductive mechanisms of several invertebrates. Among the reproductive alterations, <i>Wolbachia</i> also causes cytoplasmic incompatibility that leads to embryo death when infected males are crossed with uninfected females, thus selecting infected females. However, the presence of <i>Wolbachia</i> has important fitness costs and infected <i>Drosophila simulans</i> males produce less sperm than their uninfected counterparts. Such sperm suffer, indeed, of some structural alterations that hinder their proper function. We took advantage of the fact that several sperm have abnormal distal regions of the tail, in which the plasma membrane is broken and the axonemal components splayed, making the ultrastructural aspects clearly observable. We found that axoneme reduction in the distal region of the sperm does not follow a unique pattern as observed in other insects, but occurs by losing accessory tubules or peripheral doublets. The axonemal tubules contain distinct coaxial ring-like structures that are still observed after axoneme fragmentation and form large clusters of several units.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 4","pages":"234-241"},"PeriodicalIF":2.4,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule shaft integrity emerges as a crucial determinant of the acetylation pattern","authors":"Mireia Andreu-Carbó,&nbsp;Cornelia Egoldt,&nbsp;Charlotte Aumeier","doi":"10.1002/cm.21887","DOIUrl":"10.1002/cm.21887","url":null,"abstract":"&lt;p&gt;The dynamic nature of microtubules extends beyond the traditional view of these structures merely growing and shortening at their ends. The concept of shaft dynamics introduces a new perspective, focusing away from the ends. Microtubules can be damaged by dissociation of tubulin dimers along the shaft, which can be repaired by incorporating new tubulin dimers, thus restoring structural integrity. These repair sites can function as rescue sites, allowing depolymerizing microtubules to stop shortening and initiate regrowth, thereby prolonging microtubule lifespan (Andreu-Carbó et al., &lt;span&gt;2022&lt;/span&gt;; Aumeier et al., &lt;span&gt;2016&lt;/span&gt;). While damage can occur spontaneously, it can also be induced locally by mechanical forces and proteins like severing enzymes and motor proteins (Andreu-Carbó et al., &lt;span&gt;2022&lt;/span&gt;; Budaitis et al., &lt;span&gt;2022&lt;/span&gt;; Schaedel et al., &lt;span&gt;2015&lt;/span&gt;, &lt;span&gt;2019&lt;/span&gt;; Triclin et al., &lt;span&gt;2021&lt;/span&gt;; Vemu et al., &lt;span&gt;2018&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;Transient shaft damage provides entry points for proteins to access the microtubule lumen. Indeed, the microtubule lumen can be occupied by several proteins, such as MAP6 and the acetyltransferase αTAT1 (Cuveillier et al., &lt;span&gt;2020&lt;/span&gt;; Szyk et al., &lt;span&gt;2014&lt;/span&gt;). αTAT1 acts in the microtubule lumen by acetylating the lysine 40 residue of α-tubulin (L'Hernaul &amp; Rosenbaum, &lt;span&gt;1985&lt;/span&gt;; Soppina et al., &lt;span&gt;2012&lt;/span&gt;), a post-translational modification (PTM) that affects microtubules' mechanical properties and interactions with molecular motors (Bulinski et al., &lt;span&gt;1988&lt;/span&gt;; Cai et al., &lt;span&gt;2009&lt;/span&gt;; Guardia et al., &lt;span&gt;2016&lt;/span&gt;; Piperno et al., &lt;span&gt;1987&lt;/span&gt;; Reed et al., &lt;span&gt;2006&lt;/span&gt;; Tas et al., &lt;span&gt;2017&lt;/span&gt;; Webster &amp; Borisy, &lt;span&gt;1989&lt;/span&gt;). For this modification, the enzymes responsible for adding or removing an acetyl group must access the lumen. While studies have focused on microtubule acetylation and how αTAT1 enters the lumen, microtubules can also be deacetylated by histone deacetylase 6 (HDAC6), which removes the acetyl group (Hubbert et al., &lt;span&gt;2002&lt;/span&gt;; Skoge &amp; Ziegler, &lt;span&gt;2016&lt;/span&gt;; Zhang et al., &lt;span&gt;2003&lt;/span&gt;). Although the exact mechanism by which HDAC6 accesses the microtubule lumen remains elusive, the discontinuous acetylation pattern in microtubules suggests a coordinated interplay between αTAT1 and HDAC6, implying that HDAC6 might enter the lumen similarly to αTAT1.&lt;/p&gt;&lt;p&gt;In a recent study, we showed that the pattern of microtubule acetylation in cells depends on the presence and distribution of microtubule damage. Specifically, microtubules are deacetylated around these damage sites. This suggests that HDAC6 enters the microtubule lumen through damages along the shaft and locally deacetylates tubulin around damage sites. Artificial increase in shaft damage through overexpression of running kinesin-1 decreases acetylation levels by shortening the acetylated segments alo","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 1-2","pages":"55-57"},"PeriodicalIF":2.4,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Septin complexes: Ahead of the curve","authors":"Mitsutoshi Nakamura,&nbsp;Susan M. Parkhurst","doi":"10.1002/cm.21890","DOIUrl":"10.1002/cm.21890","url":null,"abstract":"<p>Individual cells have robust repair systems to survive cell cortex damage caused by mechanical and chemical stresses, allowing them to maintain the integrity of tissues and organs. The contraction of an actomyosin ring at the wound edge is a major mechanism for physically closing the cell wound. In contrast to polymerization and bundling of actin filaments, little is known about how linear actin filaments are bent to be integrated into the actin ring structure encircling the wound edge. We recently found that the five <i>Drosophila</i> Septins function simultaneously in the regulation of actomyosin ring assembly, contraction, and disassembly during cell wound repair. These Septins form two distinct complexes—Sep1-Sep2-Pnut and Sep4-Sep5-Pnut—composed of different subunits from the same groups. Strikingly, these two distinct Septin complexes have different degrees of F-actin bending activities that are consistent with their spatial recruitment: different degrees of curved actin filaments are required for the robust formation of different regions of the actomyosin ring. In addition, we found that the two Septin complexes are regulated by different molecular pathways as a loss of Anillin only affects Sep1-Sep2-Pnut complex recruitment. These findings open new directions for how individual Septin subunits form complexes and function differentially in cellular and developmental processes.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 4","pages":"229-233"},"PeriodicalIF":2.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and function of FAP47 in the central pair apparatus of Chlamydomonas flagella","authors":"Yuma Tani,&nbsp;Haruaki Yanagisawa,&nbsp;Toshiki Yagi,&nbsp;Masahide Kikkawa","doi":"10.1002/cm.21882","DOIUrl":"10.1002/cm.21882","url":null,"abstract":"<p>Motile cilia have a so-called “9 + 2” structure, which consists of nine doublet microtubules and a central pair apparatus. The central pair apparatus (CA) is thought to interact mechanically with radial spokes and to control the flagellar beating. Recently, the components of the CA have been identified by proteomic and genomic analyses. Still, the mechanism of how the CA contributes to ciliary motility has much to be revealed. Here, we focused on one CA component with a large molecular weight: FAP47, and its relationship with two other CA components with large molecular weight: HYDIN, and CPC1. The analyses of motility of the <i>Chlamydomonas</i> mutants revealed that in contrast to <i>cpc1</i> or <i>hydin</i>, which swam more slowly than the wild type, <i>fap47</i> cells displayed wild-type swimming velocity and flagellar beat frequency, yet interestingly, <i>fap47</i> cells have phototaxis defects and swim straighter than the wild-type cells. Furthermore, the double mutant <i>fap47cpc1</i> and <i>fap47hydin</i> showed significantly slower swimming than <i>cpc1</i> and <i>hydin</i> cells, and the motility defect of <i>fap47cpc1</i> was rescued to the <i>cpc1</i> level with GFP-tagged FAP47, indicating that the lack of FAP47 makes the motility defect of <i>cpc1</i> worse. Cryo-electron tomography demonstrated that the <i>fap47</i> lacks a part of the C1–C2 bridge of CA. Taken together, these observations indicate that FAP47 maintains the structural stiffness of the CA, which is important for flagellar regulation.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"81 11","pages":"669-680"},"PeriodicalIF":2.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.21882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single molecule visualization of tropomyosin isoform organization in the mammalian actin cytoskeleton","authors":"Maria L. Cagigas,&nbsp;Nicholas Ariotti,&nbsp;Jeff Hook,&nbsp;James Rae,&nbsp;Robert G. Parton,&nbsp;Nicole S. Bryce,&nbsp;Peter W. Gunning,&nbsp;Edna C. Hardeman","doi":"10.1002/cm.21883","DOIUrl":"10.1002/cm.21883","url":null,"abstract":"<p>The actin cytoskeleton is composed of both branched and unbranched actin filaments. In mammals, the unbranched actin filaments are primarily copolymers of actin and tropomyosin. Biochemical and imaging studies indicate that different tropomyosin isoforms are segregated to different actin filament populations in cells and tissues, providing isoform-specific functionality to the actin filament. Intrinsic to this model is the prediction that single-molecule imaging of tropomyosin isoforms would confirm homopolymer formation along the length of single actin filaments, a knowledge gap that remains unaddressed in the cellular environment. We combined chemical labeling of genetically engineered tropomyosin isoforms with electron tomography to locate individual tropomyosin molecules in fibroblasts. We find that the organization of two non-muscle tropomyosins, Tpm3.1 with Tpm4.2, can be distinguished from each other using light and electron microscopy. Visualization of single tropomyosin molecules associated with actin filaments supports the hypothesis that tropomyosins form continuous homopolymers, instead of heteropolymers, in the presence of all physiologically native actin-binding proteins. This is true for both isoforms tested. Furthermore, the data suggest that the tropomyosin molecules on one side of an actin filament may not be in register with those on the opposite side, indicating that each tropomyosin polymer may assembly independently.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 1-2","pages":"45-54"},"PeriodicalIF":2.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEK inhibitors and DA-Raf, a dominant-negative antagonist of the Ras–ERK pathway, prevent the migration and invasion of KRAS-mutant cancer cells","authors":"Aoi Matsuda,&nbsp;Ryuichi Masuzawa,&nbsp;Kazuya Takahashi,&nbsp;Kazunori Takano,&nbsp;Takeshi Endo","doi":"10.1002/cm.21881","DOIUrl":"10.1002/cm.21881","url":null,"abstract":"<p>The Ras-induced ERK pathway (Raf–MEK–ERK signaling cascade) regulates a variety of cellular responses including cell proliferation, survival, and migration. Activating mutations in <i>RAS</i> genes, particularly in the <i>KRAS</i> gene, constitutively activate the ERK pathway, resulting in tumorigenesis, cancer cell invasion, and metastasis. DA-Raf1 (DA-Raf) is a splicing isoform of A-Raf and contains the Ras-binding domain but lacks the kinase domain. Consequently, DA-Raf antagonizes the Ras–ERK pathway in a dominant-negative manner and can serve as a tumor suppressor that targets mutant Ras protein-induced tumorigenesis. We show here that MEK inhibitors and DA-Raf interfere with the in vitro collective cell migration and invasion of human <i>KRAS</i>-mutant carcinoma cell lines, the lung adenocarcinoma A549, colorectal carcinoma HCT116, and pancreatic carcinoma MIA PaCa-2 cells. DA-Raf expression was silenced in these cancer cell lines. All these cell lines had high collective migration abilities and invasion properties in Matrigel, compared with nontumor cells. Their migration and invasion abilities were impaired by suppressing the ERK pathway with the MEK inhibitors U0126 and trametinib, an approved anticancer drug. Expression of DA-Raf in MIA PaCa-2 cells reduced the ERK activity and hindered the migration and invasion abilities. Therefore, DA-Raf may function as an invasion suppressor protein in the <i>KRAS</i>-mutant cancer cells by blocking the Ras–ERK pathway when DA-Raf expression is induced in invasive cancer cells.</p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"82 1-2","pages":"32-44"},"PeriodicalIF":2.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front Cover Image","authors":"","doi":"10.1002/cm.21885","DOIUrl":"https://doi.org/10.1002/cm.21885","url":null,"abstract":"<p>ON THE FRONT COVER: MCF-7 cells treated with compound 2 (published in this issue) and Colchicine and stained with α-tubulin antibody for immunofluorescence (pseudo coloured). Credit: Jianhong Yang (Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy. West China Hospital, Sichuan University, Chengdu, China)\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"81 6-7","pages":"C1"},"PeriodicalIF":2.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.21885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Back Cover Image","authors":"","doi":"10.1002/cm.21886","DOIUrl":"https://doi.org/10.1002/cm.21886","url":null,"abstract":"<p>ON THE BACK COVER: HeLa cells expressing stable EGFP-α-tubulin were treated with 10 εM Cevipabulin for 1 min and monitored for tubulin using confocal fluorescence microscopy. Credit: Jianhong Yang (Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy. West China Hospital, Sichuan University, Chengdu, China)\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":55186,"journal":{"name":"Cytoskeleton","volume":"81 6-7","pages":"C4"},"PeriodicalIF":2.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cm.21886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}