Cytoskeleton (Hoboken, N.J.)最新文献

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Isoform Specificity of a Compound Targeting Actin Filaments Containing Tropomyosin Tpm1.8/1.9. 一种靶向含有原肌球蛋白Tpm1.8/1.9的肌动蛋白细丝的化合物的异构体特异性
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-14 DOI: 10.1002/cm.70055
Jeff Hook, Edna C Hardeman, Peter W Gunning
{"title":"Isoform Specificity of a Compound Targeting Actin Filaments Containing Tropomyosin Tpm1.8/1.9.","authors":"Jeff Hook, Edna C Hardeman, Peter W Gunning","doi":"10.1002/cm.70055","DOIUrl":"https://doi.org/10.1002/cm.70055","url":null,"abstract":"<p><p>The unbranched actin filaments in mammalian cells are usually composed of co-polymers of a specific tropomyosin isoform with actin. Genetic manipulation has revealed that the tropomyosins largely define the functional properties of actin filaments in an isoform-specific, non-redundant manner. Tropomyosin isoforms play a role in human diseases including cancers, thrombocytopenia and thrombocythaemia, endometrial decidualisation resistance, and ulcerative colitis. Hence, the development of compounds that target different tropomyosins are potentially valuable tools for cell biology as well as potential therapeutics. We have recently identified compounds that target Tpm1.8/1.9 and now address the isoform specificity of these compounds. Tpm1.8/1.9 is primarily enriched in the lamellipodium of migrating cells but not in stress fibre bundles unlike Tpm3.1/3.2 and Tpm4.2, which are enriched in stress fibres. Human fibroblasts also incorporate Tpm1.8/1.9 into fine filaments emanating from the perinuclear region. Exposure of human fibroblasts and SK-N-SH cells to the compounds 189-1 and 189-3 results in dispersal of Tpm1.8/1.9 from the lamellipodium and fine filaments to a diffuse organisation in the cytoplasm. In contrast, at doses that disperse Tpm1.8/1.9, 189-3 has no impact on the association of either Tpm3.1/3.2 or Tpm4.2 with actin filament bundles, whereas 189-1 also targets Tpm4.2. Tpm1.8/1.9 organisation becomes dispersed between 12- and 18-hour exposure to 189-3, and the organisation of Tpm1.8/1.9 returns within 4 h of drug washout. We conclude that the amino acid sequence differences located at 7 positions in the first 19 residues of these isoforms provide sufficient specificity to generate compounds that target Tpm1.8/1.9 alone.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287914","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 Cilia-Associated Protein CCDC89 Is Dispensable for Male Fertility in Mice. 纤毛相关蛋白CCDC89在小鼠雄性生殖能力中是不可或缺的。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-11 DOI: 10.1002/cm.70057
Dehao Song, Qingchao Li, Yuqing Sun, Huijie Zhao, Ting Song
{"title":"The Cilia-Associated Protein CCDC89 Is Dispensable for Male Fertility in Mice.","authors":"Dehao Song, Qingchao Li, Yuqing Sun, Huijie Zhao, Ting Song","doi":"10.1002/cm.70057","DOIUrl":"https://doi.org/10.1002/cm.70057","url":null,"abstract":"<p><p>Cilia are microtubule-based organelles that protrude from the cell surface and are crucial for cellular sensory and motility functions. Defects in cilia are associated with various diseases, collectively known as ciliopathies. Although single-cell transcriptomics and proteomics have identified many proteins linked to cilia, their physiological roles remain largely unclear. In this study, we identify coiled-coil domain-containing 89 (CCDC89) as a new ciliary protein. Super-resolution imaging reveals that CCDC89 localizes to the axonemal lumen in motile cilia of mouse ependymal multiciliated cells. However, no apparent morphological abnormalities are observed in the lung and brain of Ccdc89 knockout mice. While CCDC89 is highly abundant in the testis, Ccdc89 knockout mice appear to have normal male fertility. Overall, our findings suggest that CCDC89 is dispensable for male fertility in mice, providing valuable information for other researchers to avoid unnecessary detailed studies.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276806","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
A Cell Type-Specific Role for Tubb6 in Ciliogenesis of Xenopus Epidermal Multiciliated Cells. Tubb6在爪蟾表皮多纤毛细胞纤毛发生中的细胞类型特异性作用。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-11 DOI: 10.1002/cm.70056
Xiaolu Xu, Jean Ross, Fiona Clark, Shuo Wei, Jian Sun
{"title":"A Cell Type-Specific Role for Tubb6 in Ciliogenesis of Xenopus Epidermal Multiciliated Cells.","authors":"Xiaolu Xu, Jean Ross, Fiona Clark, Shuo Wei, Jian Sun","doi":"10.1002/cm.70056","DOIUrl":"10.1002/cm.70056","url":null,"abstract":"<p><p>Cilia are microtubule-based organelles found on the surface of most eukaryotic cells. These microtubules are composed of α- and β-tubulin heterodimers, and different tubulin isotypes can confer distinct properties to microtubules. Despite their importance, the contribution of individual tubulin isotype to cilia formation and function remains largely unexplored in vertebrates. Here, we identify a critical role for the β-tubulin isotype Tubb6 in the formation of motile cilia in Xenopus epidermal multiciliated cells (MCCs). Tubb6 mRNA is selectively expressed in MCCs, and its protein product localizes to ciliary axonemes. Loss of Tubb6 leads to a marked reduction in cilia number and length, resulting in defective MCC function. In contrast, mono-motile cilia in the gastrocoel roof plate are unaffected by Tubb6 depletion, suggesting a selective requirement for ciliogenesis in MCCs. Together, our findings uncover a cell type-specific role for Tubb6 in motile cilia formation and highlight the functional specialization of tubulin isotypes in vertebrate cilia assembly.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276842","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 New Nexin-Dynein Regulatory Complex Component CCDC153 Is Dispensable for Ciliary Motility and Fertility in Mice. 新的连接蛋白-动力蛋白调节复合物CCDC153是小鼠纤毛运动和生育不可缺少的成分。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-08 DOI: 10.1002/cm.70053
Shanshan Nai, Yanjie Zheng, Xunshuo Liu, Huijie Zhao
{"title":"The New Nexin-Dynein Regulatory Complex Component CCDC153 Is Dispensable for Ciliary Motility and Fertility in Mice.","authors":"Shanshan Nai, Yanjie Zheng, Xunshuo Liu, Huijie Zhao","doi":"10.1002/cm.70053","DOIUrl":"https://doi.org/10.1002/cm.70053","url":null,"abstract":"<p><p>The nexin-dynein regulatory complex (N-DRC) is an essential axonemal structure for ciliary and flagellar motility. Coiled-coil domain containing 153 (CCDC153) has recently been identified as a new N-DRC component in Tetrahymena thermophila. However, the physiological function of its mammalian homolog remains unknown. Here, we generated a Ccdc153 knockout mouse model and explored its functional association with motile cilia. We found that CCDC153 was highly expressed in the motile cilia-abundant tissues and localized to the axonemal lumen in motile cilia. However, Ccdc153 knockout mice were viable and exhibited normal brain ventricles and fertility. Overall, our results suggest that CCDC153 is dispensable for ciliary motility in brain ventricles and sperm movement, indicating that CCDC153 is not a potential causative gene in human ciliopathies.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253910","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
Andrea Lacigová.
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-07 DOI: 10.1002/cm.70054
Andrea Lacigová
{"title":"Andrea Lacigová.","authors":"Andrea Lacigová","doi":"10.1002/cm.70054","DOIUrl":"https://doi.org/10.1002/cm.70054","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240466","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
Author Profile: Dr. Harshita Kasera. 作者简介:Harshita Kasera博士。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-10-04 DOI: 10.1002/cm.70049
Harshita Kasera
{"title":"Author Profile: Dr. Harshita Kasera.","authors":"Harshita Kasera","doi":"10.1002/cm.70049","DOIUrl":"https://doi.org/10.1002/cm.70049","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226393","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
Novel Pathogenic Biallelic Variants in KIAA0586 Expand the Variant Spectrum of Ciliopathies. KIAA0586中新的致病双等位基因变异扩展了纤毛病的变异谱。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-09-29 DOI: 10.1002/cm.70047
Yue Shen, Ruida He, Chao Lu, Ziheng Wang, Yufei Yu, Zongfu Cao, Minna Luo
{"title":"Novel Pathogenic Biallelic Variants in KIAA0586 Expand the Variant Spectrum of Ciliopathies.","authors":"Yue Shen, Ruida He, Chao Lu, Ziheng Wang, Yufei Yu, Zongfu Cao, Minna Luo","doi":"10.1002/cm.70047","DOIUrl":"https://doi.org/10.1002/cm.70047","url":null,"abstract":"<p><p>Joubert syndrome (JBTS) is a group of recessive neurodevelopmental disorders classified as a specific type of ciliopathy with genetic heterogeneity. JBTS23, a subtype of Joubert syndrome, is caused by variations in the KIAA0586 gene. In this study, we report a 9-month-old boy diagnosed with JBTS based on the presence of the molar tooth sign in the midbrain and global developmental delay. Whole-exome sequencing identified two pathogenic variants in KIAA0586 (c.3944 T>G and c.3686 + 3A>G), consistent with an autosomal recessive inheritance pattern. These findings were confirmed through Sanger sequencing of the proband and his parents. This study identifies two novel pathogenic variants in KIAA0586, provides a genetic diagnosis for this patient as JBTS23, and expands the variant spectrum of KIAA0586 associated with JBTS.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187737","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
Molecular Insights Into the Differential Binding Affinity of Human Katanin Hexamer for C-Terminal Tails of β-Tubulin Isotypes. 人Katanin六聚体对β-微管蛋白同型c端尾的差异结合亲和力的分子观察。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-09-26 DOI: 10.1002/cm.70046
Purva Khodke, Vibhuti Saxena, Pruthanka Patil, Bajarang Vasant Kumbhar
{"title":"Molecular Insights Into the Differential Binding Affinity of Human Katanin Hexamer for C-Terminal Tails of β-Tubulin Isotypes.","authors":"Purva Khodke, Vibhuti Saxena, Pruthanka Patil, Bajarang Vasant Kumbhar","doi":"10.1002/cm.70046","DOIUrl":"https://doi.org/10.1002/cm.70046","url":null,"abstract":"<p><p>Katanin is a microtubule-severing enzyme critical for cellular processes such as cell division, migration, signaling, and cellular homeostasis. Katanin, a heterodimeric protein composed of p60 and p80, exhibits ATPase activity that is stimulated by microtubules and is responsible for removing tubulin subunits during severing. This severing function requires the assembly of katanin into a hexameric complex. Previous studies have demonstrated that katanin has a differential binding affinity towards C-terminal tails (CTTs) of β-tubulin isotypes. However, the interaction dynamics of human katanin hexamer with different β-tubulin isotypes-especially those overexpressed in various carcinomas-remain poorly understood at the atomic level. In this study, we employed homology modeling, docking, and molecular dynamics simulations to examine the binding behavior of the human katanin hexamer with the CTTs of five β-tubulin isotypes, which include βI, βIIa, βIII, βIVb, and βV. Our findings reveal that the katanin hexamer exhibits distinct interaction patterns with each isotype, attributed to their sequence-specific variations in the CTTs. Detailed MD analyses, including radius of gyration, solvent-accessible surface area, hydrogen bonding, principal component analysis, and free energy landscape profiling, further support these isoform-specific differences in the interaction dynamics. Moreover, binding free energy calculations indicate that the hexamer shows the highest affinity for βIIa, followed by βIII, βIVb, and βV, with the weakest interaction observed for βI. These computational insights underscore the mechanism of isoform-specific binding preferences of the human katanin hexamer toward β-tubulin CTTs, highlighting their potential implications for therapeutic targeting in cancer contexts where specific β-tubulin isotypes are upregulated.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151976","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
Introduction to the Special Issue "Centrosomes to Cilia: In Sickness and in Health". 特刊《中心体到纤毛:疾病与健康》导言。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-09-24 DOI: 10.1002/cm.70045
Priyanka Singh
{"title":"Introduction to the Special Issue \"Centrosomes to Cilia: In Sickness and in Health\".","authors":"Priyanka Singh","doi":"10.1002/cm.70045","DOIUrl":"https://doi.org/10.1002/cm.70045","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132783","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
TUBA4A: The Tale of an Unconventional Tubulin. TUBA4A:非常规微管蛋白的故事。
IF 1.6
Cytoskeleton (Hoboken, N.J.) Pub Date : 2025-09-18 DOI: 10.1002/cm.70044
Jia-Lin Zhu, Xin Liang
{"title":"TUBA4A: The Tale of an Unconventional Tubulin.","authors":"Jia-Lin Zhu, Xin Liang","doi":"10.1002/cm.70044","DOIUrl":"https://doi.org/10.1002/cm.70044","url":null,"abstract":"<p><p>Microtubules are highly adaptable cytoskeletal polymers whose dynamic nature supports a broad spectrum of cellular activities. Their dynamic behavior is regulated by an intricate network of factors, including tubulin isotypes and post-translational modifications. Together, these elements shape the properties of microtubules in response to both intrinsic and extrinsic cues. Within this regulatory landscape, the \"tubulin code\" has been proposed as a conceptual framework to explain how subtle molecular variations shape context-specific microtubule functions. Among mammalian α-tubulin isotypes, TUBA4A is characterized by the unique C-terminal tail, distinct biochemical behaviors, enriched expression in multiple tissues (e.g., in the central nervous system) and emerging roles in neurodegeneration. This review summarizes the molecular and physiological features of TUBA4A, highlights its potential contributions to normal neuronal function and neurological disorders, and offers perspectives for future studies.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082614","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
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