Journal of Cell Biology最新文献_第2页

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

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

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

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

CNTD1 is crucial for crossover formation in female meiosis and for establishing the ovarian reserve. CNTD1在女性减数分裂的交叉形成和卵巢储备的建立中起着至关重要的作用。

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.202401021

Anna J Wood, Rania M Ahmed, Leah E Simon, Rachel A Bradley, Stephen Gray, Ian D Wolff, Paula E Cohen

{"title":"CNTD1 is crucial for crossover formation in female meiosis and for establishing the ovarian reserve.","authors":"Anna J Wood, Rania M Ahmed, Leah E Simon, Rachel A Bradley, Stephen Gray, Ian D Wolff, Paula E Cohen","doi":"10.1083/jcb.202401021","DOIUrl":"10.1083/jcb.202401021","url":null,"abstract":"In meiotic prophase I, hundreds of DNA double-strand breaks are formed and subsequently repaired as noncrossovers or crossovers (COs). COs are essential for accurate chromosome segregation during the first meiotic division, and errors in this process result in aneuploidy, birth defects, or infertility. Such errors are more pronounced in females compared with males, indicating that CO regulation and surveillance are sexually dimorphic. We demonstrate here dual roles of cyclin N-terminal domain containing 1 (CNTD1) in ensuring appropriate CO between homologous chromosomes in oocytes and in establishing the pool of follicles in the postnatal ovary. CNTD1-deficient oocytes fail to form COs and exhibit a severely depleted follicle pool shortly after birth, which is temporally distinct from previously reported CO mutants. Further investigation indicates that follicle loss is CHK2-dependent, resulting from inappropriate retention of HORMAD1 and the absence of SKP1. These findings indicate that CNTD1 plays novel roles in CO designation and establishment of the follicular reserve in female mammals.","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/PMC12147665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248073","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 substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1. Parkin的底物相互作用区域指导线粒体GTPase Miro1的泛素化。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-27 DOI: 10.1083/jcb.202408025

Joanna Koszela, Anne Rintala-Dempsey, Giulia Salzano, Viveka Pimenta, Outi Kamarainen, Mads Gabrielsen, Aasna L Parui, Gary S Shaw, Helen Walden

{"title":"A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1.","authors":"Joanna Koszela, Anne Rintala-Dempsey, Giulia Salzano, Viveka Pimenta, Outi Kamarainen, Mads Gabrielsen, Aasna L Parui, Gary S Shaw, Helen Walden","doi":"10.1083/jcb.202408025","DOIUrl":"10.1083/jcb.202408025","url":null,"abstract":"Mutations in the E3 ubiquitin ligase Parkin gene have been linked to early onset Parkinson's disease. Besides many other roles, Parkin is involved in clearance of damaged mitochondria via mitophagy-a process of particular importance in dopaminergic neurons. Upon mitochondrial damage, Parkin accumulates at the outer mitochondrial membrane and is activated, leading to ubiquitination of many mitochondrial substrates and recruitment of mitophagy effectors. While the activation mechanisms of autoinhibited Parkin have been extensively studied, it remains unknown how Parkin recognizes its substrates for ubiquitination. Here, we characterize a conserved region in the flexible linker between the Ubl and RING0 domains of Parkin, which is indispensable for Parkin interaction with the mitochondrial GTPase Miro1. Our results may explain fast kinetics of Miro1 ubiquitination by Parkin in recombinant assays and provide a biochemical explanation for Miro1-dependent Parkin recruitment to the mitochondrial membrane observed in cells. Our findings are important for understanding mitochondrial homeostasis and may inspire new therapeutic avenues for Parkinson's disease.","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/PMC12203984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505823","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 biotin-HaloTag ligand enables efficient affinity capture of protein variants from live cells. 生物素-卤素标签配体能够有效地从活细胞中捕获蛋白质变体。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-07-16 DOI: 10.1083/jcb.202410025

Anoop Kumar Yadav,Abhijeet S Jadhav,Pawel M Szczepanik,Paolo Fagherazzi,Ivo Kabelka,Robert Vácha,Jakub Svenda,Hana Polasek-Sedlackova

{"title":"A biotin-HaloTag ligand enables efficient affinity capture of protein variants from live cells.","authors":"Anoop Kumar Yadav,Abhijeet S Jadhav,Pawel M Szczepanik,Paolo Fagherazzi,Ivo Kabelka,Robert Vácha,Jakub Svenda,Hana Polasek-Sedlackova","doi":"10.1083/jcb.202410025","DOIUrl":"https://doi.org/10.1083/jcb.202410025","url":null,"abstract":"HaloTag technology represents a versatile tool for studying proteins. Fluorescent HaloTag ligands employed in sequential labeling led to the discovery of distinct protein variants for histones, cohesins, and MCM complexes. However, an efficient biochemical approach to separate these distinct protein variants to study their biological functions is missing. Principally, being a gap in technology, the HaloTag toolbox lacks affinity ligands displaying good cell permeability and efficient affinity capture. Here, we describe the design, synthesis, and validation of a new cell-permeable biotin-HaloTag ligand, which allows rapid labeling of Halo-tagged proteins in live cells and their efficient separation using streptavidin pull-down. We provide a proof-of-concept application of how to use the herein-developed affinity ligand in sequential labeling to biochemically separate protein variants and study their biological properties. This approach enables to address fundamental questions concerning essential cellular processes, including genome duplication and chromatin maintenance.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"109 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640201","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

Microtubule nucleation: How the NEDD1:MZT1:GCP3 trio captures the γ-TuRC. 微管成核：NEDD1:MZT1:GCP3三人组如何捕获γ-TuRC。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-07-15 DOI: 10.1083/jcb.202506019

Clémence Paumier,Cécile Sauvanet,Benoît Gigant

引用次数: 0

Myosin 15 participates in assembly and remodeling of the presynapse. 肌凝蛋白15参与突触前的组装和重塑。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-07-08 DOI: 10.1083/jcb.202305059

Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist

{"title":"Myosin 15 participates in assembly and remodeling of the presynapse.","authors":"Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist","doi":"10.1083/jcb.202305059","DOIUrl":"https://doi.org/10.1083/jcb.202305059","url":null,"abstract":"The assembly and remodeling of presynaptic specializations are of crucial importance for circuit development and adaptive behaviors. However, the mechanisms by which presynaptic material is locally distributed within synaptic terminals and across consuming active zones remain poorly understood. In this study, we identify the conserved unconventional class XV myosin, Myo15, an actin motor, as a novel regulator of presynaptic assembly and remodeling in Drosophila. Myo15 localizes to the local actin and microtubule network at synaptic terminals. Depletion of Myo15 resulted in smaller individual active zones, increased active zone density, and irregular terminal morphology, while its overexpression enlarged individual active zones and promoted synaptic terminal growth. Myo15 was found to modulate the actin meshwork, and deletion of its microtubule-binding MyTH4 domain rendered the protein nonfunctional. Furthermore, Myo15 was essential for presynaptic functional homeostatic plasticity and memory consolidation. These findings suggest that Myo15 plays a critical role in the assembly and remodeling of presynaptic active zones.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"47 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578795","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