Journal of cell science最新文献

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Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules. 线粒体未折叠蛋白反应的激活调节应激颗粒的动态形成。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-05-01 Epub Date: 2024-12-05 DOI: 10.1242/jcs.263548
Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker
{"title":"Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules.","authors":"Marta Lopez-Nieto, Zhaozhi Sun, Emily Relton, Rahme Safakli, Brian D Freibaum, J Paul Taylor, Alessia Ruggieri, Ioannis Smyrnias, Nicolas Locker","doi":"10.1242/jcs.263548","DOIUrl":"10.1242/jcs.263548","url":null,"abstract":"<p><p>To rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that the SG formation and UPRmt pathways are intertwined and communicate. UPRmt induction results in eIF2α phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. The induction of GADD34 (also known as PPP1R15A) during late UPRmt protects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial functions and cellular survival are enhanced during UPRmt activation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmt that might contribute to restoring mitochondrial functions under stressful conditions.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-20 DOI: 10.1242/jcs.263660
Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey
{"title":"Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres.","authors":"Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey","doi":"10.1242/jcs.263660","DOIUrl":"https://doi.org/10.1242/jcs.263660","url":null,"abstract":"<p><p>The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy human hamstring muscles for confocal microscopy (n=6) and RNAscope in situ hybridisation (n=6) to gain insight into the profiles of cells and myonuclei in this region, in a fibre type manner. A marked presence of mononuclear cells was observed coating the myofibre tips (confirmed by serial block face scanning electron microscopy and cryosection immunofluorescence), with higher numbers for type I (median 29; range 16-63) than type II (16; 9-23) myofibres (p<0.05). The number of these cells expressing COL22A1 was comparable between fibre types. Myonuclear number and density gradually increased from the myofibre proper towards the tip for both fibre types (p<0.05). COL22A1 was expressed by similar proportions of myonuclei in type I (median 26%; range 13-56) and type II (19%; 3-67) myofibre tips. 70% of the COL22A1+ nuclei in the MTJ region were myonuclei, and the remaining 30% were MTJ cells. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fis1 regulates mitochondrial morphology, bioenergetics, and removal of mtDNA damage in irradiated glioblastoma cells.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-20 DOI: 10.1242/jcs.263459
Yuli Buckley, Maria S K Stoll, Charles L Hoppel, Jason A Mears
{"title":"Fis1 regulates mitochondrial morphology, bioenergetics, and removal of mtDNA damage in irradiated glioblastoma cells.","authors":"Yuli Buckley, Maria S K Stoll, Charles L Hoppel, Jason A Mears","doi":"10.1242/jcs.263459","DOIUrl":"https://doi.org/10.1242/jcs.263459","url":null,"abstract":"<p><p>In response to external stress, mitochondrial dynamics is often disrupted, but the associated physiologic changes are often uncharacterized. In many cancers, including glioblastoma (GBM), mitochondrial dysfunction has been observed. Understanding how mitochondrial dynamics and physiology contribute to treatment resistance will lead to more targeted and effective therapeutics. This study aims to uncover how mitochondria in GBM cells adapt to and resist ionizing radiation (IR), a component of the standard of care for GBM. Using several approaches, we investigated how mitochondrial dynamics and physiology adapt to radiation stress and uncover a novel role for Fis1, a pro-fission protein, in regulating the stress response through mitochondrial DNA (mtDNA) maintenance and altered mitochondrial bioenergetics. Importantly, our data demonstrate that increased fission in response to IR leads to removal of mtDNA damage and more efficient oxygen consumption through altered ETC activities in intact mitochondria. These findings demonstrate a key role for Fis1 in targeting damaged mtDNA for degradation and regulating mitochondrial bioenergetics through altered dynamics.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ankyrin-B is required for the establishment and maintenance of lens cytoarchitecture, mechanics and clarity. Ankyrin-B 是建立和维持晶状体细胞结构、力学和透明度所必需的。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-18 DOI: 10.1242/jcs.262349
Rupalatha Maddala, Ariana Allen, Nikolai P Skiba, Ponugoti Vasantha Rao
{"title":"Ankyrin-B is required for the establishment and maintenance of lens cytoarchitecture, mechanics and clarity.","authors":"Rupalatha Maddala, Ariana Allen, Nikolai P Skiba, Ponugoti Vasantha Rao","doi":"10.1242/jcs.262349","DOIUrl":"10.1242/jcs.262349","url":null,"abstract":"<p><p>The transparent ocular lens is essential for vision because it focuses light onto the retina. Despite recognition of the importance of its unique cellular architecture and mechanical properties, the molecular mechanisms governing these attributes remain elusive. This study aims to elucidate the role of ankyrin-B (AnkB, encoded by ANK2), a membrane scaffolding protein, in lens cytoarchitecture, growth and function using a conditional knockout (cKO) mouse model. The AnkB cKO mouse has no defects in lens morphogenesis but exhibited changes that supported a global role for AnkB in maintenance of lens clarity, size, cytoarchitecture, membrane organization and stiffness. Notably, absence of AnkB led to nuclear cataract formation, which was evident from postnatal day 16. AnkB cKO lens fibers exhibit progressive disruption in membrane organization of the spectrin-actin cytoskeleton, cell adhesion proteins and channel proteins; loss and degradation of several membrane proteins [such as NrCAM. N-cadherin (CDH2) and aquaporin-0 (also known as MIP)]; along with a disorganized plasma membrane and impaired membrane interdigitations. Furthermore, absence of AnkB led to decreased lens stiffness. Collectively, these results illustrate the essential role for AnkB in lens architecture, growth and function through its involvement in membrane skeletal and protein organization and stability.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apical integrins as a switchable target to regulate the epithelial barrier. 顶端整合素是调节上皮屏障的可切换目标。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/jcs.263580
Raven J Peterson, Ryan C Reed, Colin R Zamecnik, Marwa A Sallam, Joel A Finbloom, Francisco J Martinez, Joshua M Levy, Aekkacha Moonwiriyakit, Tejal A Desai, Michael Koval
{"title":"Apical integrins as a switchable target to regulate the epithelial barrier.","authors":"Raven J Peterson, Ryan C Reed, Colin R Zamecnik, Marwa A Sallam, Joel A Finbloom, Francisco J Martinez, Joshua M Levy, Aekkacha Moonwiriyakit, Tejal A Desai, Michael Koval","doi":"10.1242/jcs.263580","DOIUrl":"10.1242/jcs.263580","url":null,"abstract":"<p><p>Tight junctions regulate epithelial barrier function and have been shown to be influenced by multiple classes of proteins. Apical integrins have been identified as potential regulators of epithelial barrier function; however, only indirect approaches have been used to measure integrin regulation of the epithelial barrier. Here, we used polymeric nanowires conjugated with anti-integrin β1 antibodies to specifically target apically localized integrins in either their closed or open conformation. Barrier regulation by apical integrins was found to be conformation specific. Nanowires targeting integrins in the closed conformation increased epithelial permeability and caused zonula occludens-1 (ZO-1, also known as TJP1) to change from a linear to a ruffled morphology. Claudin-2 and claudin-4 colocalized with ZO-1 and were also ruffled; however, claudin-1 and claudin-7 remained linear. Ruffling was dependent on myosin light chain kinases (MLCKs) and Rho kinases (ROCKs). Conversely, targeting integrins in the open conformation decreased epithelial permeability and made junctions more linearized. Anti-integrin β1 nanowires differentially affected actin and talin (analyzed using pan-talin antibodies), depending on whether they contained activating or inhibitory antibodies. Thus, apical integrins can act as a conformation-sensitive switch that regulates epithelial barrier function.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fantastic proteins and where to find them - histones, in the nucleus and beyond.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/jcs.262071
Johanna Grinat, Noah P Shriever, Maria A Christophorou
{"title":"Fantastic proteins and where to find them - histones, in the nucleus and beyond.","authors":"Johanna Grinat, Noah P Shriever, Maria A Christophorou","doi":"10.1242/jcs.262071","DOIUrl":"https://doi.org/10.1242/jcs.262071","url":null,"abstract":"<p><p>Animal genomes are packaged into chromatin, a highly dynamic macromolecular structure of DNA and histone proteins organised into nucleosomes. This accommodates packaging of lengthy genomic sequences within the physical confines of the nucleus while also enabling precise regulation of access to genetic information. However, histones existed before chromatin and have lesser-known functions beyond genome regulation. Most notably, histones are potent antimicrobial agents, and the release of chromatin to the extracellular space is a defence mechanism nearly as ancient and widespread as chromatin itself. Histone sequences have changed very little throughout evolution, suggesting the possibility that some of their 'non-canonical' functions are at play in parallel or in concert with their genome regulatory functions. In this Review, we take an evolutionary perspective of histone, nuclear chromatin and extracellular chromatin biology and describe the known extranuclear and extracellular functions of histones. We detail molecular mechanisms of chromatin release and extracellular chromatin sensing, and we discuss their roles in physiology and disease. Finally, we present evidence and give a perspective on the potential of extracellular histones to act as bioactive, cell modulatory factors.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 24","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mutations in the DNA processivity factor POL30 predisposes the FLO11 locus to epigenetic instability in S. cerevisiae. DNA 过程因子 PCNA(POL30)的突变易导致 FLO11 基因座的表观遗传不稳定。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-17 DOI: 10.1242/jcs.262006
Safia Mahabub Sauty, Ashley Fisher, Andrew Dolson, Krassimir Yankulov
{"title":"Mutations in the DNA processivity factor POL30 predisposes the FLO11 locus to epigenetic instability in S. cerevisiae.","authors":"Safia Mahabub Sauty, Ashley Fisher, Andrew Dolson, Krassimir Yankulov","doi":"10.1242/jcs.262006","DOIUrl":"10.1242/jcs.262006","url":null,"abstract":"<p><p>The FLO genes in Saccharomyces cerevisiae are repressed by heterochromatin formation, involving histone deacetylases, transcription factors and non-coding RNAs. Here, we report that mutations in the processivity factor POL30 (PCNA) that show transient derepression at the subtelomeres and the mating-type loci do not derepress FLO loci. However, deletions of the replisome stability factors RRM3 and TOF1 along with pol30 mutations induced flocculation phenotypes. The phenotypes correlated with increased expression of reporter proteins driven by the FLO11 promoter, the frequency of silent to active conversions of FLO11, and reduced expression of the regulatory long non-coding RNAs ICR1 and PWR1. Alterations in the local replication landscape of FLO11 indicate a link between defects in the fork protection complex and the stability of gene silencing. Analyses of these mutants at the subtelomeres and the HMLα locus showed a similar derepression phenotype and suggest transient instability of both active and silent states of FLO11. We conclude that RRM3 and TOF1 interact differentially with the pol30 mutations to promote transient derepression or complete epigenetic conversions of FLO11. We suggest that the interaction between POL30, RRM3 and TOF1 is essential to maintain epigenetic stability at the studied loci.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-20 DOI: 10.1242/jcs.262036
Rafael Lucena, Akshi Jasani, Steph Anastasia, Douglas Kellogg, Maria Alcaide-Gavilan
{"title":"Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.","authors":"Rafael Lucena, Akshi Jasani, Steph Anastasia, Douglas Kellogg, Maria Alcaide-Gavilan","doi":"10.1242/jcs.262036","DOIUrl":"https://doi.org/10.1242/jcs.262036","url":null,"abstract":"<p><p>Tor kinases play diverse and essential roles in control of nutrient signaling and cell growth. These kinases are assembled into two multiprotein complexes known as TORC1 and TORC2. In budding yeast, TORC2 relays nutrient-dependent signals that strongly influence growth rate and cell size. However, the mechanisms that control TORC2 signaling are poorly understood. Activation of TORC2 requires Mss4, a phosphatidylinositol 4-phosphate 5-kinase that recruits and activates downstream targets of TORC2. Localization of Mss4 to the plasma membrane is thought to be controlled by phosphorylation, and previous work has suggested that yeast homologs of casein kinase 1, Yck1 and Yck2 (referred to here collectively as Yck1/2), Control phosphorylation of Mss4. Here, we generated a new analog-sensitive allele of YCK2 and used it to test whether Yck1/2 influence localization of Mss4 or signaling in the TORC2 network. We found that Yck1/2 strongly influence Mss4 phosphorylation and localization, as well as influencing regulation of multiple components of the TORC2 network. However, inhibition of Yck1/2 causes mild effects on the best-characterized signaling axis in the TORC2 pathway, suggesting that Yck1/2 might play a larger role in influencing less well-understood aspects of TORC2 signaling.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 24","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TXNDC15, an ER-localized thioredoxin-like transmembrane protein, contributes to ciliary transition zone integrity.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-16 DOI: 10.1242/jcs.262123
Shingo Yamazaki, Taiju Fujii, Shuhei Chiba, Hye-Won Shin, Kazuhisa Nakayama, Yohei Katoh
{"title":"TXNDC15, an ER-localized thioredoxin-like transmembrane protein, contributes to ciliary transition zone integrity.","authors":"Shingo Yamazaki, Taiju Fujii, Shuhei Chiba, Hye-Won Shin, Kazuhisa Nakayama, Yohei Katoh","doi":"10.1242/jcs.262123","DOIUrl":"https://doi.org/10.1242/jcs.262123","url":null,"abstract":"<p><p>Primary cilia have specific proteins on their membrane to fulfill their sensory functions. Preservation of the specific protein composition of cilia relies on the barrier function of the transition zone (TZ) located at the ciliary base. Defects in cilia and the TZ cause ciliopathies, which have diverse clinical manifestations, including Meckel syndrome (MKS). Many of the proteins mutated in individuals with MKS are known to constitute the MKS module of the TZ. Although TXNDC15 (also known as MKS14) is a thioredoxin-related transmembrane protein that is localized mainly in the endoplasmic reticulum (ER) and is mutated in individuals with MKS, its role at the TZ or within cilia has not been characterized. Here, we show that TXNDC15-knockout cells have defects in MKS module assembly and in ciliary membrane protein localization. These defects in TXNDC15-knockout cells were not rescued by exogenous expression of any of the TXNDC15 constructs with MKS variations in the thioredoxin domain. Furthermore, TXNDC15 with mutations of two cysteine residues within the thioredoxin domain failed to rescue defects in TXNDC15-knockout cells, suggesting that TXNDC15 controls the TZ integrity from outside the TZ via its thioredoxin domain.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 24","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An evolutionary perspective on the relationship between kinetochore size and CENP-E dependence for chromosome alignment.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-19 DOI: 10.1242/jcs.263466
Ana C Almeida, Helder Rocha, Maximilian W D Raas, Hanh Witte, Ralf J Sommer, Berend Snel, Geert J P L Kops, Reto Gassmann, Helder Maiato
{"title":"An evolutionary perspective on the relationship between kinetochore size and CENP-E dependence for chromosome alignment.","authors":"Ana C Almeida, Helder Rocha, Maximilian W D Raas, Hanh Witte, Ralf J Sommer, Berend Snel, Geert J P L Kops, Reto Gassmann, Helder Maiato","doi":"10.1242/jcs.263466","DOIUrl":"https://doi.org/10.1242/jcs.263466","url":null,"abstract":"<p><p>Chromosome alignment during mitosis can occur as a consequence of bi-orientation or is assisted by the CENP-E (kinesin-7) motor at kinetochores. We previously found that Indian muntjac chromosomes with larger kinetochores bi-orient more efficiently and are biased to align in a CENP-E-independent manner, suggesting that CENP-E dependence for chromosome alignment negatively correlates with kinetochore size. Here, we used targeted phylogenetic profiling of CENP-E in monocentric (localized centromeres) and holocentric (centromeres spanning the entire chromosome length) clades to test this hypothesis at an evolutionary scale. We found that, despite being present in common ancestors, CENP-E was lost more frequently in taxa with holocentric chromosomes, such as Hemiptera and Nematoda. Functional experiments in two nematodes with holocentric chromosomes in which a CENP-E ortholog is absent (Caenorhabditis elegans) or present (Pristionchus pacificus) revealed that targeted expression of human CENP-E to C. elegans kinetochores partially rescued chromosome alignment defects associated with attenuated polar-ejection forces, whereas CENP-E inactivation in P. pacificus had no detrimental effects on mitosis and viability. These data showcase the dispensability of CENP-E for mitotic chromosome alignment in species with larger kinetochores.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 24","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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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