Journal of Cell Biology最新文献_第6页

SOD1 is delivered to lysosomes via autophagy to maintain lysosomal function and integrity. SOD1通过自噬传递到溶酶体，以维持溶酶体的功能和完整性。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-08-07 DOI: 10.1083/jcb.202501007

Yanzhe Zheng,Meng Li,Xuelin Chen,Ze Zheng,Zixuan Chen,Ruilin Tian,Yan G Zhao

引用次数: 0

Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex. 结合γ-微管蛋白环复合物的微管锚定因子NEDD1的结构。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-05-21 DOI: 10.1083/jcb.202410206

Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek

{"title":"Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex.","authors":"Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek","doi":"10.1083/jcb.202410206","DOIUrl":"10.1083/jcb.202410206","url":null,"abstract":"The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule-organizing centers (MTOCs) by the evolutionarily conserved attachment factor NEDD1. However, the structural basis of the NEDD1-γ-TuRC interaction is not known. Here, we report cryo-EM structures of NEDD1 bound to the human γ-TuRC in the absence or presence of the activating factor CDK5RAP2. We found that the C-terminus of NEDD1 forms a tetrameric α-helical assembly that contacts the lumen of the γ-TuRC cone and orients its microtubule-binding domain away from the complex. The structure of the γ-TuRC simultaneously bound to NEDD1 and CDK5RAP2 reveals that both factors can associate with the \"open\" conformation of the complex. Our results show that NEDD1 does not induce substantial conformational changes in the γ-TuRC but suggest that anchoring of γ-TuRC-capped microtubules by NEDD1 would be structurally compatible with the significant conformational changes experienced by the γ-TuRC during microtubule nucleation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110599","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

A coordinated kinase and phosphatase network regulates Stu2 recruitment to yeast kinetochores. 一个协调的激酶和磷酸酶网络调节着Stu2向酵母着丝点的募集。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-27 DOI: 10.1083/jcb.202410196

Michael G Stewart, Joseph S Carrier, Jacob A Zahm, Stephen C Harrison, Matthew P Miller

{"title":"A coordinated kinase and phosphatase network regulates Stu2 recruitment to yeast kinetochores.","authors":"Michael G Stewart, Joseph S Carrier, Jacob A Zahm, Stephen C Harrison, Matthew P Miller","doi":"10.1083/jcb.202410196","DOIUrl":"10.1083/jcb.202410196","url":null,"abstract":"Cells coordinate diverse events at anaphase onset, including separase activation, cohesin cleavage, chromosome separation, and spindle reorganization. Regulation of the XMAP215 family member and microtubule polymerase, Stu2, at the metaphase-anaphase transition determines a redistribution from kinetochores to spindle microtubules. We show that cells modulate Stu2 kinetochore-microtubule localization by Polo-like kinase1/Cdc5-mediated phosphorylation of T866, near the Stu2 C-terminus, thereby promoting dissociation from the kinetochore Ndc80 complex. Cdk/Cdc28 likely primes Cdc5:Stu2 interaction. Cdc28 activity is also required for Stu2 nuclear import. PP2ACdc55 actively opposes Cdc5 activity on Stu2T866 during metaphase. This counter-regulation allows for switch-like redistribution of Stu2pT866 at anaphase onset when separase inhibits PP2ACdc55. Blocking Stu2T866 phosphorylation disrupts anaphase spindle progression, and we infer that PP2ACdc55 regulates the mitotic spindle by dephosphorylating multiple MAPs, including Stu2. These data support a model in which increased phosphorylation at anaphase onset results from phosphatase inhibition and point to a larger regulatory network that facilitates rapid cytoskeletal modulation required for anaphase spindle function.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505822","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

Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway. CK2调控Ran通路驱动减数分裂和有丝分裂纺锤体形态的变化。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-07-01 DOI: 10.1083/jcb.202407154

Helena Cantwell, Hieu Nguyen, Arminja N Kettenbach, Rebecca Heald

{"title":"Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway.","authors":"Helena Cantwell, Hieu Nguyen, Arminja N Kettenbach, Rebecca Heald","doi":"10.1083/jcb.202407154","DOIUrl":"10.1083/jcb.202407154","url":null,"abstract":"The transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug treatment approach using Ciona eggs and found that inhibition of casein kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in Xenopus egg cytoplasmic extracts. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences between Xenopus meiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors, inducing mitotic spindle morphology.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540342","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

Correction: Phosphorylation of p66Shc and forkhead proteins mediates Aβ toxicity. 更正：p66Shc和叉头蛋白的磷酸化介导了Aβ毒性。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-07-02 DOI: 10.1083/jcb.20041004106232025c

Wanli W Smith, Darrell D Norton, Myriam Gorospe, Haibing Jiang, Shino Nemoto, Nikki J Holbrook, Toren Finkel, John W Kusiak

引用次数: 0

Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs. 蜕皮激素调节发育中的果蝇卵上皮细胞吞噬细胞的命运。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-05-28 DOI: 10.1083/jcb.202411073

Gaurab Ghosh, Devyan Das, Abhrajyoti Nandi, Souvik De, Sreeramaiah N Gangappa, Mohit Prasad

{"title":"Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs.","authors":"Gaurab Ghosh, Devyan Das, Abhrajyoti Nandi, Souvik De, Sreeramaiah N Gangappa, Mohit Prasad","doi":"10.1083/jcb.202411073","DOIUrl":"10.1083/jcb.202411073","url":null,"abstract":"Acquisition of nonprofessional phagocytic cell fate plays an important role in sculpting functional metazoan organs and maintaining overall tissue homeostasis. Though physiologically highly relevant, how the normal epithelial cells acquire phagocytic fate is still mostly unclear. We have employed the Drosophila ovary model to demonstrate that the classical ecdysone signaling in the somatic epithelial follicle cells (AFCs) aids the removal of germline nurse cells (NCs) in late oogenesis. Our live-cell imaging data reveal a novel phenomenon wherein collective behavior of 4-5 AFCs is required for clearing a single NC. By employing classical genetics, molecular biology, and yeast one-hybrid assay, we demonstrate that ecdysone modulates the phagocytic disposition of AFCs at two levels. It regulates the epithelial-mesenchymal transition of the AFCs through Serpent and modulates the phagocytic behavior of the AFCs through Croquemort and Draper. Our data provide unprecedented novel molecular insights into how ecdysone signaling reprograms AFCs toward a phagocytic fate.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159236","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

The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1. 帕金森病相关DJ-1糖酵解副产物降解的反应机制

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-04 DOI: 10.1083/jcb.202411078

Aiko Watanabe, Shizuka Ogiwara, Mirei Saito, Masaki Mishima, Masahiro Yamashina, Ryuichiro Ishitani, Yutaka Ito, Keiji Tanaka, Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoshitaka Moriwaki, Noriyuki Matsuda

{"title":"The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1.","authors":"Aiko Watanabe, Shizuka Ogiwara, Mirei Saito, Masaki Mishima, Masahiro Yamashina, Ryuichiro Ishitani, Yutaka Ito, Keiji Tanaka, Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoshitaka Moriwaki, Noriyuki Matsuda","doi":"10.1083/jcb.202411078","DOIUrl":"10.1083/jcb.202411078","url":null,"abstract":"DJ-1/PARK7 is the causative gene for hereditary recessive Parkinson's disease. Recent studies have reported that DJ-1 hydrolyzes cyclic 3-phosphoglyceric anhydride (cPGA), a highly reactive metabolite. However, the molecular mechanisms underlying cPGA hydrolase activity have yet to be fully elucidated. To gain a more comprehensive understanding of this activity in DJ-1, we performed molecular simulations that predicted how DJ-1 recognizes and hydrolyzes cPGA. The accuracy of these structural predictions was validated through systematic mutational analyses exemplified by loss of activity with the A107P mutation. Although DJ-1 possesses both cPGA hydrolase and α-oxoaldehyde hydratase activities in vitro, we confirmed that DJ-1 dysfunction caused an increase in cPGA-derived modifications but had no effect on α-oxoaldehyde-derived modifications in cells. Importantly, A107 and P158, pathogenic missense mutation sites found in Parkinson's disease patients, are critical for cPGA hydrolysis both in vitro and in cells. The evidence-based catalytic mechanism for DJ-1 hydrolysis of cPGA that we propose here explains their pathophysiological significance.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215940","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

Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. 微转移的代谢适应改变了EV的产生，从而产生侵入性微环境。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-09 DOI: 10.1083/jcb.202405061

Michalis Gounis, America V Campos, Engy Shokry, Louise Mitchell, Ruhi Deshmukh, Emmanuel Dornier, Nicholas Rooney, Sandeep Dhayade, Luis Pardo, Madeleine Moore, David Novo, Jenna Mowat, Craig Jamieson, Emily Kay, Sara Zanivan, Nikki R Paul, Claire Mitchell, Colin Nixon, Iain Macpherson, Saverio Tardito, David Sumpton, Karen Blyth, Jim C Norman, Cassie J Clarke

{"title":"Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments.","authors":"Michalis Gounis, America V Campos, Engy Shokry, Louise Mitchell, Ruhi Deshmukh, Emmanuel Dornier, Nicholas Rooney, Sandeep Dhayade, Luis Pardo, Madeleine Moore, David Novo, Jenna Mowat, Craig Jamieson, Emily Kay, Sara Zanivan, Nikki R Paul, Claire Mitchell, Colin Nixon, Iain Macpherson, Saverio Tardito, David Sumpton, Karen Blyth, Jim C Norman, Cassie J Clarke","doi":"10.1083/jcb.202405061","DOIUrl":"10.1083/jcb.202405061","url":null,"abstract":"Altered cellular metabolism has been associated with the acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model of mammary carcinoma with syngeneic transplantation and primary tumor resection to generate isogenic cells from primary tumors and their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic cells increase proline production at the expense of glutathione synthesis, leading to a reduction in total glutathione levels. Micrometastatic cells also have altered sphingomyelin metabolism, leading to increased intracellular levels of specific ceramides. The combination of these metabolic adaptations alters extracellular vesicle (EV) production to render the microenvironment more permissive for invasion. Indeed, micrometastatic cells shut down Rab27-dependent production of EVs and, instead, switch on neutral sphingomyelinase-2 (nSM2)-dependent EV release. EVs released in an nSM2-dependent manner from micrometastatic cells, in turn, influence the ability of fibroblasts to deposit extracellular matrix, which promotes cancer cell invasiveness. These data provide evidence that metabolic rewiring drives invasive processes in metastasis by influencing EV release.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248074","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

Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity. 锥形肽束f -肌动蛋白在立体纤毛支点实现最佳终身机械敏感性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-05 DOI: 10.1083/jcb.202408026

Inna A Belyantseva, Chang Liu, Abigail K Dragich, Takushi Miyoshi, Sayaka Inagaki, Ayesha Imtiaz, Risa Tona, Karen Sofia Zuluaga-Osorio, Shadan Hadi, Elizabeth Wilson, Eva Morozko, Rafal Olszewski, Rizwan Yousaf, Yuliya Sokolova, Gavin P Riordan, S Andrew Aston, Atteeq U Rehman, Cristina Fenollar Ferrer, Jan Wisniewski, Shoujun Gu, Gowri Nayak, Richard J Goodyear, Jinan Li, Jocelyn F Krey, Talah Wafa, Rabia Faridi, Samuel Mawuli Adadey, Meghan Drummond, Benjamin Perrin, Dennis C Winkler, Matthew F Starost, Hui Cheng, Tracy Fitzgerald, Guy P Richardson, Lijin Dong, Peter G Barr-Gillespie, Michael Hoa, Gregory I Frolenkov, Thomas B Friedman, Bo Zhao

{"title":"Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity.","authors":"Inna A Belyantseva, Chang Liu, Abigail K Dragich, Takushi Miyoshi, Sayaka Inagaki, Ayesha Imtiaz, Risa Tona, Karen Sofia Zuluaga-Osorio, Shadan Hadi, Elizabeth Wilson, Eva Morozko, Rafal Olszewski, Rizwan Yousaf, Yuliya Sokolova, Gavin P Riordan, S Andrew Aston, Atteeq U Rehman, Cristina Fenollar Ferrer, Jan Wisniewski, Shoujun Gu, Gowri Nayak, Richard J Goodyear, Jinan Li, Jocelyn F Krey, Talah Wafa, Rabia Faridi, Samuel Mawuli Adadey, Meghan Drummond, Benjamin Perrin, Dennis C Winkler, Matthew F Starost, Hui Cheng, Tracy Fitzgerald, Guy P Richardson, Lijin Dong, Peter G Barr-Gillespie, Michael Hoa, Gregory I Frolenkov, Thomas B Friedman, Bo Zhao","doi":"10.1083/jcb.202408026","DOIUrl":"10.1083/jcb.202408026","url":null,"abstract":"Stereocilia are rod-like mechanosensory projections consisting of unidirectionally oriented actin filaments that extend into the inner ear hair cell cytoskeleton, forming dense rootlets. Taperin (TPRN) localizes to the narrowed-down base of stereocilia, where they pivot in response to sound and gravity. We show that TPRN-deficient mice have progressive deafness characterized by gradual asynchronous retraction and fusion of outer and inner hair cell stereocilia, followed by synaptic abnormalities. Stereocilia that lack TPRN develop warped rootlets with gradual loss of TRIOBP-5 and ANKRD24 from mechanosensory rows starting postnatally. In contrast, TPRN overexpression causes excessive F-actin bundling, extra rows, and over-elongation of stereocilia during development. Purified full-length mouse TPRN cross-links F-actin into bendable bundles reflecting in vivo data. This F-actin-bundling ability is attributed to the TPRN N-terminal region. TPRN interacts with the membrane receptor PTPRQ, connecting the F-actin core to the plasma membrane, stabilizing stereocilia. Thus, TPRN is a specialized F-actin bundler strategically located to augment stereocilia rootlet formation and their pivot point flexibility for sustained sound-induced deflections.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225562","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

Alternative to the statistical mass confusion of testing for "no effect". 替代“无效果”测试的统计质量混淆。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-07-23 DOI: 10.1083/jcb.202403034

Josh L Morgan

引用次数: 0