Journal of cell science最新文献_第10页

Casein kinase 1 controls components of a TORC2 signaling network in budding yeast. 酪蛋白激酶1控制出芽酵母中TORC2信号网络的组成部分。

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":"10.1242/jcs.262036","url":null,"abstract":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795287/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMPK associates with and causes fragmentation of the Golgi by phosphorylating the guanine nucleotide exchange factor GBF1. AMPK 通过磷酸化鸟嘌呤核苷酸交换因子 GBF1 与高尔基体结合并导致其破碎。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-23 DOI: 10.1242/jcs.262182

Jordana B Freemantle, Mhairi C Towler, Emma R Hudson, Thomas Macartney, Monika Zwirek, David J K Liu, David A Pan, Sreenivasan Ponnambalam, D Grahame Hardie

{"title":"AMPK associates with and causes fragmentation of the Golgi by phosphorylating the guanine nucleotide exchange factor GBF1.","authors":"Jordana B Freemantle, Mhairi C Towler, Emma R Hudson, Thomas Macartney, Monika Zwirek, David J K Liu, David A Pan, Sreenivasan Ponnambalam, D Grahame Hardie","doi":"10.1242/jcs.262182","DOIUrl":"10.1242/jcs.262182","url":null,"abstract":"AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular functions in response to changes in energy availability. However, whether AMPK activity is spatially regulated, and the implications for cell function, have been unclear. We now report that AMPK associates with the Golgi, and that its activation by two specific pharmacological activators leads to Golgi fragmentation similar to that caused by the antibiotic Golgicide A, an inhibitor of Golgi-specific Brefeldin A resistance factor-1 (GBF1), a guanine nucleotide exchange factor that targets ADP-ribosylation factor 1 (ARF1). Golgi fragmentation in response to AMPK activators is lost in cells carrying gene knockouts of AMPK-α subunits. AMPK has been previously reported to phosphorylate GBF1 at residue Thr1337, and its activation causes phosphorylation at that residue. Importantly, Golgi disassembly upon AMPK activation is blocked in cells expressing a non-phosphorylatable GBF1-T1337A mutant generated by gene editing. Furthermore, the trafficking of a plasma membrane-targeted protein through the Golgi complex is delayed by AMPK activation. Our findings provide a mechanism to link AMPK activation during cellular energy stress to downregulation of protein trafficking involving the Golgi.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutations in the DNA processivity factor POL30 predispose 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 predispose 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":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827858/pdf/","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":"OA","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. TXNDC15是一种内质网定位的硫氧还蛋白样跨膜蛋白，有助于纤毛过渡带的完整性。

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":"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.","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. 着丝粒大小与染色体对CENP-E依赖性关系的进化观点。

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":"10.1242/jcs.263466","url":null,"abstract":"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.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827601/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biphasic DNA damage and non-canonical replication stress response govern radiation-induced senescence in glioblastoma. 双相 DNA 损伤和非规范复制应激反应控制着胶质母细胞瘤的辐射诱导衰老。

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.261844

Atanu Ghorai, Bhawna Singh, Shilpee Dutt

{"title":"Biphasic DNA damage and non-canonical replication stress response govern radiation-induced senescence in glioblastoma.","authors":"Atanu Ghorai, Bhawna Singh, Shilpee Dutt","doi":"10.1242/jcs.261844","DOIUrl":"10.1242/jcs.261844","url":null,"abstract":"Therapy-induced senescence (TIS) in glioblastoma (GBM) residual disease and escape from TIS account for resistance and recurrence, but the mechanism of TIS manifestation remains obscure. Here, we demonstrate that replication stress (RS) is critical for the induction of TIS in residual cells by employing an in vitro GBM therapy-resistance cellular model. Interestingly, we found a 'biphasic' mode of DNA damage after radiation treatment and reveal that the second phase of DNA damage arises majorly in the S phase of residual cells due to RS. Mechanistically, we show that persistent phosphorylated ATR is a safeguard for radiation resilience, whereas the other canonical RS molecules remain unaltered during the second phase of DNA damage. Importantly, RS preceded the induction of senescence, and ATR inhibition resulted in TIS reduction, leading to apoptosis. Moreover, ATR inhibition sensitized PARP-1 inhibitor-induced enhanced TIS-mediated resistance, leading to cell death. Our study demonstrates the crucial role of RS in TIS induction and maintenance in GBM residual cells, and targeting ATR alone or in combination with a PARP-1 inhibitor will be an effective strategy to eliminate TIS for better treatment outcomes.","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":"142681886","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

How to reduce your lab's carbon footprint. 如何减少实验室的碳足迹。

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.263722

Julie Welburn

引用次数: 0

Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation. 剪切应力刺激的 AMPK 将内皮细胞力学、新陈代谢和血管扩张联系在一起。

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.262232

Nicholas M Cronin, Logan W Dawson, Kris A DeMali

引用次数: 0

Regulation of miR-206 in denervated and dystrophic muscles, and its effect on acetylcholine receptor clustering. 变性肌肉和肌营养不良肌肉中 MiR-206 的调控及其对 AChR 聚类的影响

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/jcs.262303

Joseph Barden, Olivia Kosloski, Amir Jadidian, Mohammed Akaaboune

{"title":"Regulation of miR-206 in denervated and dystrophic muscles, and its effect on acetylcholine receptor clustering.","authors":"Joseph Barden, Olivia Kosloski, Amir Jadidian, Mohammed Akaaboune","doi":"10.1242/jcs.262303","DOIUrl":"10.1242/jcs.262303","url":null,"abstract":"The muscle-specific microRNA miR-206 has recently emerged as a potential regulator of genes involved in the formation and regeneration of the neuromuscular junction (NMJ). This study investigated miR-206-3p (miR-206) expression in synaptic and non-synaptic regions of denervated mice and α-dystrobrevin (Dtna)-knockout mice, as well as its impact on the formation and/or maintenance of agrin-induced acetylcholine receptor (AChR) clusters. In denervated, Dtna-deficient and crushed muscles, miR-206 expression significantly increased compared to what was seen for innervated muscles. Although miR-206 expression was slightly elevated in the synaptic regions of innervated muscles, it was dramatically increased in non-synaptic areas of denervated muscles. miR-206 targets transcripts of essential NMJ proteins, such as Dtna, α-syntrophin (Snta1) and rapsyn, but not the AChRα subunit (encoded by Chrna1) or Lrp4 in innervated muscles. However, in denervated muscles, AChRα transcripts, which increased significantly, become a target of miR-206. Co-expression of miR-206 with rapsyn, Dtna and Snta1 in C2C12 myoblasts significantly reduced their protein levels, and overexpression of miR-206 in myotubes disrupted agrin-induced AChR clustering. These results indicate that miR-206 fine-tunes NMJ signaling proteins by regulating transcripts of various proteins with different localizations under normal and pathological conditions.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase separation of microtubule-binding proteins - implications for neuronal function and disease. 微管结合蛋白的相分离--对神经元功能和疾病的影响

IF 3.3 3区生物学

Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-13 DOI: 10.1242/jcs.263470

Daisy Duan, Anthony J Koleske

引用次数: 0