Journal of Cell Biology最新文献_第10页

Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends.

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-01-23 DOI: 10.1083/jcb.202406061

Saishree S Iyer,Fangrui Chen,Funso E Ogunmolu,Shoeib Moradi,Vladimir A Volkov,Emma J van Grinsven,Chris van Hoorn,Jingchao Wu,Nemo Andrea,Shasha Hua,Kai Jiang,Ioannis Vakonakis,Mia Potočnjak,Franz Herzog,Benoît Gigant,Nikita Gudimchuk,Kelly E Stecker,Marileen Dogterom,Michel O Steinmetz,Anna Akhmanova

{"title":"Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends.","authors":"Saishree S Iyer,Fangrui Chen,Funso E Ogunmolu,Shoeib Moradi,Vladimir A Volkov,Emma J van Grinsven,Chris van Hoorn,Jingchao Wu,Nemo Andrea,Shasha Hua,Kai Jiang,Ioannis Vakonakis,Mia Potočnjak,Franz Herzog,Benoît Gigant,Nikita Gudimchuk,Kelly E Stecker,Marileen Dogterom,Michel O Steinmetz,Anna Akhmanova","doi":"10.1083/jcb.202406061","DOIUrl":"https://doi.org/10.1083/jcb.202406061","url":null,"abstract":"Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4. We found that whereas CEP97 does not bind to microtubules directly, CP110 autonomously binds microtubule plus ends, blocks their growth, and inhibits depolymerization. Cryo-electron tomography revealed that CP110 associates with the luminal side of microtubule plus ends and suppresses protofilament flaring. CP110 directly interacts with CPAP, which acts as a microtubule polymerase that overcomes CP110-induced growth inhibition. Together, the two proteins impose extremely slow processive microtubule growth. Disruption of CP110-CPAP interaction in cells inhibits centriole elongation and increases incidence of centriole defects. Our findings reveal how two centriolar cap proteins with opposing activities regulate microtubule plus-end elongation and explain their antagonistic relationship during centriole formation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"78 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The KNL-1/Knl1 outer kinetochore protein caught regulating F-actin. KNL-1/Knl1外着丝点蛋白调控f -肌动蛋白。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-01-16 DOI: 10.1083/jcb.202412191

Hannes E Bülow

引用次数: 0

Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle. 不同的微管结合重复序列调节纺锤体内不同位置的TPX2活性。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-01-16 DOI: 10.1083/jcb.202404025

Zhuobi Liang,Junjie Huang,Yong Wang,Shasha Hua,Kai Jiang

引用次数: 0

Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress. 激活溶酶体 Ca2+ 通道可减轻线粒体损伤和氧化应激。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-05 DOI: 10.1083/jcb.202403104

Xinghua Feng, Weijie Cai, Qian Li, Liding Zhao, Yaping Meng, Haoxing Xu

{"title":"Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress.","authors":"Xinghua Feng, Weijie Cai, Qian Li, Liding Zhao, Yaping Meng, Haoxing Xu","doi":"10.1083/jcb.202403104","DOIUrl":"10.1083/jcb.202403104","url":null,"abstract":"Elevated levels of plasma-free fatty acids and oxidative stress have been identified as putative primary pathogenic factors in endothelial dysfunction etiology, though their roles are unclear. In human endothelial cells, we found that saturated fatty acids (SFAs)-including the plasma-predominant palmitic acid (PA)-cause mitochondrial fragmentation and elevation of intracellular reactive oxygen species (ROS) levels. TRPML1 is a lysosomal ROS-sensitive Ca2+ channel that regulates lysosomal trafficking and biogenesis. Small-molecule agonists of TRPML1 prevented PA-induced mitochondrial damage and ROS elevation through activation of transcriptional factor EB (TFEB), which boosts lysosome biogenesis and mitophagy. Whereas genetically silencing TRPML1 abolished the protective effects of TRPML1 agonism, TRPML1 overexpression conferred a full resistance to PA-induced oxidative damage. Pharmacologically activating the TRPML1-TFEB pathway was sufficient to restore mitochondrial and redox homeostasis in SFA-damaged endothelial cells. The present results suggest that lysosome activation represents a viable strategy for alleviating oxidative damage, a common pathogenic mechanism of metabolic and age-related diseases.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT. KPNA3通过调节NPAT的缩合和核输入来调节组蛋白位点体的形成。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-02 DOI: 10.1083/jcb.202401036

Shui Bo Xu, Xiu Kui Gao, Hao Di Liang, Xiao Xia Cong, Xu Qi Chen, Wen Kai Zou, Jia Li Tao, Zhao Yuan Pan, Jiao Zhao, Man Huang, Zhang Bao, Yi Ting Zhou, Li Ling Zheng

{"title":"KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.","authors":"Shui Bo Xu, Xiu Kui Gao, Hao Di Liang, Xiao Xia Cong, Xu Qi Chen, Wen Kai Zou, Jia Li Tao, Zhao Yuan Pan, Jiao Zhao, Man Huang, Zhang Bao, Yi Ting Zhou, Li Ling Zheng","doi":"10.1083/jcb.202401036","DOIUrl":"10.1083/jcb.202401036","url":null,"abstract":"The histone locus body (HLB) is a membraneless organelle that determines the transcription of replication-dependent histones. However, the mechanisms underlying the appropriate formation of the HLB in the nucleus but not in the cytoplasm remain unknown. HLB formation is dependent on the scaffold protein NPAT. We identify KPNA3 as a specific importin that drives the nuclear import of NPAT by binding to the nuclear localization signal (NLS) sequence. NPAT undergoes phase separation, which is inhibited by KPNA3-mediated impairment of self-association. In this, a C-terminal self-interaction facilitator (C-SIF) motif, proximal to the NLS, binds the middle 431-1,030 sequence to mediate the self-association of NPAT. Mechanistically, the anchoring of KPNA3 to the NPAT-NLS sterically blocks C-SIF motif-dependent NPAT self-association. This leads to the suppression of aberrant NPAT condensation in the cytoplasm. Collectively, our study reveals a previously unappreciated role of KPNA3 in modulating HLB formation and delineates a steric hindrance mechanism that prevents inappropriate cytoplasmic NPAT condensation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Painting lysosomes to study organelle heterogeneity. 绘制溶酶体以研究细胞器的异质性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202412011

Di Chen, Maximiliano G Gutierrez

引用次数: 0

Directed stochasticity: Building biomolecular condensates in the right place. 定向随机性：在正确的位置构建生物分子凝聚体。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-24 DOI: 10.1083/jcb.202412035

Mark S Geisler, James P Kemp, Robert J Duronio

引用次数: 0

PI(3,5)P2 asymmetry during mitosis is essential for asymmetric vacuolar inheritance. 有丝分裂过程中PI(3,5)P2的不对称性对不对称空泡遗传至关重要。

IF 4.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-08 DOI: 10.1083/jcb.202406170

Mariam Huda, Mukadder Koyuncu, Cansu Dilege, Ayse Koca Caydasi

{"title":"PI(3,5)P2 asymmetry during mitosis is essential for asymmetric vacuolar inheritance.","authors":"Mariam Huda, Mukadder Koyuncu, Cansu Dilege, Ayse Koca Caydasi","doi":"10.1083/jcb.202406170","DOIUrl":"10.1083/jcb.202406170","url":null,"abstract":"Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a low-abundance signaling lipid that plays crucial roles in various cellular processes, including endolysosomal system structure/function, stress response, and cell cycle regulation. PI(3,5)P2 synthesis increases in response to environmental stimuli, yet its behavior in cycling cells under basal conditions remains elusive. Here, we analyzed spatiotemporal changes in PI(3,5)P2 levels during the cell cycle of S. cerevisiae. We found that PI(3,5)P2 accumulates on the vacuole in the daughter cell while it disappears from the vacuole in the mother cell during mitosis. Concomitant with the changes in PI(3,5)P2 distribution, the daughter vacuole became more acidic, whereas the acidity of the mother vacuole decreased during mitosis. Our data further showed that both PI(3,5)P2 and the PI(3,5)P2 effector protein Atg18 are determinants of vacuolar-pH asymmetry and acidity. Our work, thus, identifies PI(3,5)P2 as a key factor for the establishment of vacuolar-pH asymmetry, providing insights into how the mother cell ages while the daughter cell is rejuvenated.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus. Nap1 和 Kap114 共同合成 H2A-H2B，促进组蛋白在细胞核中的定向释放。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-27 DOI: 10.1083/jcb.202408193

Ho Yee Joyce Fung, Jenny Jiou, Ashley B Niesman, Natalia E Bernardes, Yuh Min Chook

{"title":"Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus.","authors":"Ho Yee Joyce Fung, Jenny Jiou, Ashley B Niesman, Natalia E Bernardes, Yuh Min Chook","doi":"10.1083/jcb.202408193","DOIUrl":"10.1083/jcb.202408193","url":null,"abstract":"Core histones, synthesized and processed in the cytoplasm, must be chaperoned as they are transported into the nucleus for nucleosome assembly. The importin Kap114 transports H2A-H2B into the yeast nucleus, where RanGTP facilitates histone release. Kap114 and H2A-H2B also bind the histone chaperone Nap1, but how Nap1 and Kap114 cooperate in transport and nucleosome assembly remains unclear. Here, biochemical and structural analyses show that Kap114, H2A-H2B, and a Nap1 dimer (Nap12) associate in the absence and presence of RanGTP to form equimolar complexes. A previous study had shown that RanGTP reduces Kap114's ability to chaperone H2A-H2B, but a new cryo-EM structure of the Nap12•H2A-H2B•Kap114•RanGTP complex explains how both Kap114 and Nap12 interact with H2A-H2B, restoring its chaperoning within the assembly while effectively depositing it into nucleosomes. Together, our results suggest that Kap114 and Nap12 provide a sheltered path that facilitates the transfer of H2A-H2B from Kap114 to Nap12, ultimately directing its specific deposition into nucleosomes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis. N 蛋白中的 SARS-CoV-2 特异适应性可抑制 NF-κB 激活并改变发病机制。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202404131

Xiao Guo, Shimin Yang, Zeng Cai, Shunhua Zhu, Hongyun Wang, Qianyun Liu, Zhen Zhang, Jiangpeng Feng, Xianying Chen, Yingjian Li, Jikai Deng, Jiejie Liu, Jiali Li, Xue Tan, Zhiying Fu, Ke Xu, Li Zhou, Yu Chen

{"title":"SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis.","authors":"Xiao Guo, Shimin Yang, Zeng Cai, Shunhua Zhu, Hongyun Wang, Qianyun Liu, Zhen Zhang, Jiangpeng Feng, Xianying Chen, Yingjian Li, Jikai Deng, Jiejie Liu, Jiali Li, Xue Tan, Zhiying Fu, Ke Xu, Li Zhou, Yu Chen","doi":"10.1083/jcb.202404131","DOIUrl":"10.1083/jcb.202404131","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway. By comparing the amino acid sequences of the SARS-CoV-2 and SARS-CoV N proteins, we identified Glu-290 and Gln-349 as critical residues in the C-terminal domain (CTD) of the SARS-CoV-2 N protein, essential for its antagonistic function. These findings were further validated in a SARS-CoV-2 trans-complementation system using cellular and animal models. Our results reveal the distinctions in inflammatory responses triggered by SARS-CoV-2 and SARS-CoV, highlighting the significance of specific amino acid alterations in influencing viral pathogenicity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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