Journal of Cell Biology最新文献_第9页

A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome. 一个多功能小鼠Col4a1等位基因揭示了古尔德综合征的潜在基因治疗参数。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-25 DOI: 10.1083/jcb.202409153

Mao Mao,Yoshihiro Ishikawa,Cassandre Labelle-Dumais,Xiaowei Wang,Yien-Ming Kuo,Uma B Gaffney,Megan E Smith,Carlie N Abdala,Matthew D Lebedev,William J Paradee,Douglas B Gould

{"title":"A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome.","authors":"Mao Mao,Yoshihiro Ishikawa,Cassandre Labelle-Dumais,Xiaowei Wang,Yien-Ming Kuo,Uma B Gaffney,Megan E Smith,Carlie N Abdala,Matthew D Lebedev,William J Paradee,Douglas B Gould","doi":"10.1083/jcb.202409153","DOIUrl":"https://doi.org/10.1083/jcb.202409153","url":null,"abstract":"Basement membranes (BMs) are specialized extracellular matrix (ECM) structures essential for organ morphogenesis, architecture, and function. BM composition and properties vary between tissues, developmental stages, and disease states, and there is only a rudimentary understanding of BM dynamics. Here, we introduce a versatile mouse model carrying a multifunctional dual-color fluorescence tagged allele with knockout potential for the fundamental BM component type IV collagen alpha 1 (COL4A1). This allele enables the characterization of cell type- and time-specific contributions to BMs and the generation of a conditional Col4a1 null allele. We demonstrate the utility of this unique genetic resource in providing clinically relevant insights for individuals with Gould syndrome - a multisystem disorder caused by COL4A1 and COL4A2 mutations. We show active COL4A1 turnover in postnatal cerebrovascular BMs, identifying a potential interventional window for cerebrovascular manifestations associated with Gould syndrome. We also demonstrate that heterozygous Col4a1 deletion is significantly less pathogenic than dominant Col4a1 missense mutations, which has important implications for gene therapy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"6 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880193","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

Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease. lrrk2 -帕金森病模型中溶酶体TPC2通道破坏Ca2+进入和多巴胺能功能。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-25 DOI: 10.1083/jcb.202412055

Martina Gregori,Gustavo J S Pereira,Robert Allen,Nicholas West,Kai-Yin Chau,Xinjiang Cai,Matthew P Bostock,Stephen R Bolsover,Marco Keller,Chiao-Yin Lee,Si Hang Lei,Kirsten Harvey,Franz Bracher,Christian Grimm,Gaiti Hasan,Matthew E Gegg,Anthony H V Schapira,Sean T Sweeney,Sandip Patel

{"title":"Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.","authors":"Martina Gregori,Gustavo J S Pereira,Robert Allen,Nicholas West,Kai-Yin Chau,Xinjiang Cai,Matthew P Bostock,Stephen R Bolsover,Marco Keller,Chiao-Yin Lee,Si Hang Lei,Kirsten Harvey,Franz Bracher,Christian Grimm,Gaiti Hasan,Matthew E Gegg,Anthony H V Schapira,Sean T Sweeney,Sandip Patel","doi":"10.1083/jcb.202412055","DOIUrl":"https://doi.org/10.1083/jcb.202412055","url":null,"abstract":"Parkinson's disease results from degeneration of dopaminergic neurons in the midbrain, but the underlying mechanisms are unclear. Here, we identify novel crosstalk between depolarization-induced entry of Ca2+ and lysosomal cation release in maintaining dopaminergic neuronal function. The common disease-causing G2019S mutation in LRRK2 selectively exaggerated Ca2+ entry in vitro. Chemical and molecular strategies inhibiting the lysosomal ion channel TPC2 reversed this. Using Drosophila, which lack TPCs, we show that the expression of human TPC2 phenocopied LRRK2 G2019S in perturbing dopaminergic-dependent vision and movement in vivo. Mechanistically, dysfunction required an intact pore, correct subcellular targeting and Rab interactivity of TPC2. Reducing Ca2+ permeability with a novel biased TPC2 agonist corrected deviant Ca2+ entry and behavioral defects. Thus, both inhibition and select activation of TPC2 are beneficial. Functional coupling between lysosomal cation release and Ca2+ influx emerges as a potential druggable node in Parkinson's disease.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"32 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880195","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

Phosphorylation-dependent regional motility of the ciliary kinesin OSM-3. 纤毛运动蛋白OSM-3的磷酸化依赖性区域运动。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-24 DOI: 10.1083/jcb.202407152

Peng Huang,Guanghan Chen,Zhiwen Zhu,Shimin Wang,Zhe Chen,Yongping Chai,Wei Li,Guangshuo Ou

引用次数: 0

TMBIM-2 links neuronal mitochondrial stress to systemic adaptation via calcium signaling. TMBIM-2通过钙信号将神经元线粒体应激与系统适应联系起来。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-23 DOI: 10.1083/jcb.202503004

Yu Sun,Terytty Yang Li

引用次数: 0

Anillin mediates unilateral furrowing during cytokinesis by limiting RhoA binding to its effectors. Anillin 通过限制 RhoA 与其效应器的结合，在细胞分裂过程中介导单侧皱缩。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-22 DOI: 10.1083/jcb.202405182

Mikhail Lebedev,Fung-Yi Chan,Elisabeth Rackles,Jennifer Bellessem,Tamara Mikeladze-Dvali,Ana Xavier Carvalho,Esther Zanin

引用次数: 0

Telomeres, the nuclear lamina, and membrane remodeling: Orchestrating meiotic chromosome movements. 端粒、核薄层和膜重塑：协调减数分裂染色体的移动

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-22 DOI: 10.1083/jcb.202412135

Hiroki Shibuya

引用次数: 0

NEMF-mediated CAT tailing facilitates translocation-associated quality control. nemf介导的CAT尾迹有助于易位相关的质量控制。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-21 DOI: 10.1083/jcb.202408199

Amanda Ennis,Lihui Wang,Yue Xu,Layla Saidi,Xiaorong Wang,Clinton Yu,Sijung Yun,Lan Huang,Yihong Ye

引用次数: 0

FGFR2 residence in primary cilia is necessary for epithelial cell signaling. FGFR2在初级纤毛中的驻留是上皮细胞信号传导所必需的。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-21 DOI: 10.1083/jcb.202311030

Alexandru Nita,Sara P Abraham,Eman R Elrefaay,Bohumil Fafilek,Eliska Cizkova,Vlad Constantin Ursachi,Iva Gudernova,Adolf Koudelka,Pooja Dudeja,Tomas Gregor,Zuzana Feketova,Gustavo Rico,Katerina Svozilova,Canan Celiker,Aleksandra A Czyrek,Tomas Barta,Lukas Trantirek,Antoni Wiedlocha,Pavel Krejci,Michaela Bosakova

{"title":"FGFR2 residence in primary cilia is necessary for epithelial cell signaling.","authors":"Alexandru Nita,Sara P Abraham,Eman R Elrefaay,Bohumil Fafilek,Eliska Cizkova,Vlad Constantin Ursachi,Iva Gudernova,Adolf Koudelka,Pooja Dudeja,Tomas Gregor,Zuzana Feketova,Gustavo Rico,Katerina Svozilova,Canan Celiker,Aleksandra A Czyrek,Tomas Barta,Lukas Trantirek,Antoni Wiedlocha,Pavel Krejci,Michaela Bosakova","doi":"10.1083/jcb.202311030","DOIUrl":"https://doi.org/10.1083/jcb.202311030","url":null,"abstract":"Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues. In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor. Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"43 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857292","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-driven cell shape changes and actomyosin flow synergize to position the centrosome. 微管驱动的细胞形状改变和肌动球蛋白流动协同作用来定位中心体。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-17 DOI: 10.1083/jcb.202405126

Alexandre Schaeffer,Simona Buracco,Morgan Gazzola,Matthieu Gelin,Benoit Vianay,Chiara de Pascalis,Laurent Blanchoin,Manuel Théry

引用次数: 0

ZBTB17/MIZ1 promotes peroxisome biogenesis by transcriptional regulation of PEX13. ZBTB17/MIZ1通过转录调控PEX13促进过氧化物酶体的生物发生。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-17 DOI: 10.1083/jcb.202407198

Hongqin Liu,Xi Chen,Hanlin Wang,Guanglei Zhuang,Zheng-Jiang Zhu,Min Zhuang

{"title":"ZBTB17/MIZ1 promotes peroxisome biogenesis by transcriptional regulation of PEX13.","authors":"Hongqin Liu,Xi Chen,Hanlin Wang,Guanglei Zhuang,Zheng-Jiang Zhu,Min Zhuang","doi":"10.1083/jcb.202407198","DOIUrl":"https://doi.org/10.1083/jcb.202407198","url":null,"abstract":"Peroxisomes are integral metabolic organelles involved in both catabolic and anabolic processes in humans, with defects linked to diseases. The functions of peroxisomes are regulated at transcriptional, translational, and posttranslational levels. In this study, we employed the CRISPR/Cas9-based screening of a ubiquitin ligase library to identify regulators of human peroxisomes. We discovered that ZBTB17 (MIZ1) plays a role in regulating the import of proteins into peroxisomes. Independent of its ubiquitin ligase activity, ZBTB17/MIZ1 operates as a transcription factor to modulate the expression of key importer PEX13, influencing the localization of peroxisomal enzymes. Furthermore, metabolomic profiling reveals that knockdown of ZBTB17 or PEX13 results in similar metabolic alterations, with downregulated purine synthesis. Collectively, we identify ZBTB17 as a key regulator of peroxisomal protein import, thereby affecting peroxisomal function and nucleotide metabolism. Our findings provide insights into the multifaceted regulation of peroxisomes in complex human cells and shed light on the molecular mechanisms underlying ZBTB17's role as a transcriptional regulator.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"3 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846283","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