Journal of Cell Biology最新文献_第6页

Correction: The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B. 更正：去泛素酶USP45通过冠状蛋白1B调节肌动蛋白抑制自噬。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-04-04 DOI: 10.1083/jcb.20240701403262025c

Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen

引用次数: 0

A cortical pool of LIN-5 (NuMA) controls cytokinetic furrow formation and cytokinesis completion. 皮质LIN-5 （NuMA）池控制细胞动力学沟形成和细胞分裂完成。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-30 DOI: 10.1083/jcb.202406059

Kuheli Adhikary,Sukriti Kapoor,Sachin Kotak

引用次数: 0

Tension-induced suppression of allosteric conformational changes coordinates kinesin-1 stepping. 张力诱导的变构构象变化抑制协调运动蛋白-1步进。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-04-29 DOI: 10.1083/jcb.202501253

Tsukasa Makino,Ryo Kanada,Teppei Mori,Ken-Ichi Miyazono,Yuta Komori,Haruaki Yanagisawa,Shoji Takada,Masaru Tanokura,Masahide Kikkawa,Michio Tomishige

{"title":"Tension-induced suppression of allosteric conformational changes coordinates kinesin-1 stepping.","authors":"Tsukasa Makino,Ryo Kanada,Teppei Mori,Ken-Ichi Miyazono,Yuta Komori,Haruaki Yanagisawa,Shoji Takada,Masaru Tanokura,Masahide Kikkawa,Michio Tomishige","doi":"10.1083/jcb.202501253","DOIUrl":"https://doi.org/10.1083/jcb.202501253","url":null,"abstract":"Kinesin-1 walks along microtubules by alternating ATP hydrolysis and movement of its two motor domains (\"head\"). The detached head preferentially binds to the forward tubulin-binding site after ATP binds to the microtubule-bound head, but the mechanism preventing premature microtubule binding while the partner head awaits ATP remains unknown. Here, we examined the role of the neck linker, the segment connecting two heads, in this mechanism. Structural analyses of the nucleotide-free head revealed a bulge just ahead of the neck linker's base, creating an asymmetric constraint on its mobility. While the neck linker can stretch freely backward, it must navigate around this bulge to extend forward. We hypothesized that increased neck linker tension suppresses premature binding of the tethered head, which was supported by molecular dynamics simulations and single-molecule fluorescence assays. These findings demonstrate a tension-dependent allosteric mechanism that coordinates the movement of two heads, where neck linker tension modulates the allosteric conformational changes rather than directly affecting the nucleotide state.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"19 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889219","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

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。