Journal of Cell Biology最新文献_第2页

Swollen lysosomes grab Rabs for a CASM-free route to LRRK2 activation.

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-20 DOI: 10.1083/jcb.202610007

Suzanne R Pfeffer

引用次数: 0

Nucleolar dynamics are determined by the ordered assembly of the ribosome. 核仁动力学是由核糖体有序组装决定的。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-09 DOI: 10.1083/jcb.202605096

Jessica Sheu-Gruttadauria, Xiaowei Yan, Nico Stuurman, Riley O Ogrean, Sabrina Lin, Stephen N Floor, Ronald D Vale

{"title":"Nucleolar dynamics are determined by the ordered assembly of the ribosome.","authors":"Jessica Sheu-Gruttadauria, Xiaowei Yan, Nico Stuurman, Riley O Ogrean, Sabrina Lin, Stephen N Floor, Ronald D Vale","doi":"10.1083/jcb.202605096","DOIUrl":"10.1083/jcb.202605096","url":null,"abstract":"Ribosome biogenesis occurs in the nucleolus, a biomolecular condensate whose material properties are thought to be important for function. However, the molecular basis of nucleolar dynamics and their relationship to ribosome assembly remain incompletely understood. We present a platform for high-throughput FRAP (HiT-FRAP) and use it to screen hundreds of genes for their impact on dynamics of the nucleolar scaffold nucleophosmin (NPM1). We find that NPM1 dynamics and nucleolar morphology are sensitive to ribosome assembly state: accumulation of early pre-ribosomal intermediates slows NPM1 dynamics and compacts the condensate, while accumulation of abortive late precursors accelerates dynamics and disrupts condensate integrity. These opposing biophysical states correlate with the strength of NPM1-pre-ribosome interactions. Importantly, mutations in the NPM1 intrinsically disordered region that alter pre-ribosome binding directly tune nucleolar dynamics. These results establish that ribosomal precursor assembly state determines nucleolar material properties through the strength of scaffold-pre-ribosome interactions and introduce HiT-FRAP as a platform for interrogating condensate dynamics broadly.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912058","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

Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development. 致病性KIF1A变异破坏轴突运输并阻碍突触发育。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-07 DOI: 10.1083/jcb.202601034

Jayne Aiken, Carris Borland, Nicolas Marotta, Benjamin L Prosser, Erika L F Holzbaur

{"title":"Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development.","authors":"Jayne Aiken, Carris Borland, Nicolas Marotta, Benjamin L Prosser, Erika L F Holzbaur","doi":"10.1083/jcb.202601034","DOIUrl":"10.1083/jcb.202601034","url":null,"abstract":"The nervous system relies on billions of neurons connected through trillions of synapses to support vital functions. Despite the importance of this synaptic network, cellular mechanisms dictating synapse formation during human neurodevelopment remain unclear. Long-distance trafficking by the microtubule motor KIF1A is crucial for synaptogenesis and downstream synapse maintenance. Mutations in KIF1A cause KIF1A-associated neurological disorder (KAND). We employed isogenic gene-edited human-induced pluripotent stem cell -derived neurons to assess the effects of disparate pathogenic mutations in KIF1A on synaptic trafficking and function. Null (p.C92*) and hypoactive (p.P305L) mutations delay neurite outgrowth, mislocalize synaptic cargoes, and decrease synapse density. Conversely, a hyperactive (p.R350G) mutation supports neurite outgrowth but causes aberrant motility of synaptic vesicle precursors and deficits in microtubule-dependent presynaptic patterning. Functional analysis of neuronal activity reveals delayed synaptic maturation in loss-of-function mutations (p.P305L, p.C92*) and precocious activity in the hyperactive p.R350G mutation. These data provide insights into how KIF1A mutations with distinct molecular-level impacts lead to significant downstream synaptic deficits in human neurons.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900678","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

Visualizing the Golgi apparatus and Golgiphagy in vivo. 可视化高尔基体和体内高尔基体吞噬。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-16 DOI: 10.1083/jcb.202508151

Pengwei Zhao, Mengyuan Zhang, Rongbin Ding, Dandan Song, Wei Liu, Lingling Zhang, Yongjuan Sang, Qiming Sun

{"title":"Visualizing the Golgi apparatus and Golgiphagy in vivo.","authors":"Pengwei Zhao, Mengyuan Zhang, Rongbin Ding, Dandan Song, Wei Liu, Lingling Zhang, Yongjuan Sang, Qiming Sun","doi":"10.1083/jcb.202508151","DOIUrl":"https://doi.org/10.1083/jcb.202508151","url":null,"abstract":"The Golgi apparatus is essential for protein secretion and cellular homeostasis, yet its organization and turnover in living tissues remain poorly understood. Golgiphagy, the selective autophagic degradation of the Golgi, has emerged as a key quality control pathway, but its physiological regulation in vivo remains largely unknown. Here, we generated two reporter mouse lines for constitutive or Cre-dependent visualization of Golgi architecture and Golgiphagy, enabling quantitative single-cell analysis across tissues. These models revealed striking cell type- and tissue-specific heterogeneity in basal Golgiphagy, including higher activity in renal proximal than distal tubules and in cerebellar than cortical neurons. Starvation and lipopolysaccharide-induced inflammation also promoted Golgi remodeling and Golgiphagy in multiple organs, particularly the liver, spleen, and kidney. Together, these reporter mice provide a powerful genetic toolkit for studying Golgi dynamics in vivo and establish that Golgiphagy is a spatially heterogeneous and stress-responsive process under physiological conditions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976800","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

Components of an ESCRT-independent nuclear envelope assembly pathway. 独立于escrt的核包膜组装途径的组成部分。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-25 DOI: 10.1083/jcb.202601189

Emma M Sydir, M Humam Farra, Abigail L Whitford, Shea Hinojosa, Pei-Yi Kao, Joao A Paulo, Sharan Swarup, C Patrick Lusk, J Wade Harper, I-Ju Lee, David Pellman

{"title":"Components of an ESCRT-independent nuclear envelope assembly pathway.","authors":"Emma M Sydir, M Humam Farra, Abigail L Whitford, Shea Hinojosa, Pei-Yi Kao, Joao A Paulo, Sharan Swarup, C Patrick Lusk, J Wade Harper, I-Ju Lee, David Pellman","doi":"10.1083/jcb.202601189","DOIUrl":"10.1083/jcb.202601189","url":null,"abstract":"In many cells, the nuclear envelope (NE) must be reassembled after mitosis, and holes in the nuclear membrane must be sealed. During NE assembly, the NE-specific adaptor, Cmp7, recruits/activates endosomal sorting complex required for transport (ESCRT)-III proteins to mediate NE sealing. However, recent evidence suggests the presence of additional mechanisms. In a screen using the fission yeast, Schizosaccharomycesjaponicus, we recently implicated the ESCRT adaptor, Alx1, and a conserved but little-studied protein, Vid27, in Cmp7-independent NE assembly. Here, we provide direct evidence that Alx1 functions in a Cmp7- and ESCRT-independent NE assembly pathway via positive regulation of Vid27. Consistent with a role in membrane remodeling, Vid27 localizes to sites of postmitotic NE sealing and is essential in S. japonicus. Alx1 and Vid27 interact, and mutations disrupting the predicted interaction interface abolish Alx1's enhancement of Vid27 function at the NE. These findings define components of a new Cmp7- and ESCRT-independent NE assembly pathway, advancing our understanding of mechanisms that maintain the integrity of the nucleus.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038876","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

Declining centromere strength compromises meiotic chromosome segregation in aging oocytes. 老化卵母细胞中着丝粒强度的下降损害了减数分裂染色体的分离。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-19 DOI: 10.1083/jcb.202606132

Tom Lemonnier, Marie Dumont, Jiyeon Leem, Aysia Khan, Hossein Yazdkhasti, Vitaly Zimyanin, Ani Khutsaidze, Stefanie Redemann, Daniele Fachinetti, Binyam Mogessie

{"title":"Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.","authors":"Tom Lemonnier, Marie Dumont, Jiyeon Leem, Aysia Khan, Hossein Yazdkhasti, Vitaly Zimyanin, Ani Khutsaidze, Stefanie Redemann, Daniele Fachinetti, Binyam Mogessie","doi":"10.1083/jcb.202606132","DOIUrl":"10.1083/jcb.202606132","url":null,"abstract":"Maternal age is the primary risk factor for aneuploidy in mammalian oocytes, but the molecular mechanisms that preserve meiotic chromosome segregation fidelity during aging remain incompletely understood. Using ultrastructural analysis, we observe that spindle microtubules in aged mouse oocytes tend to exhibit increased misorientation and shorter interaction lengths, whereas microtubule number and density remain largely unchanged. We demonstrate that the levels of the key centromeric components CENP-A and CENP-C are reduced in oocytes from aged mice. Acute degradation of CENP-A during meiosis I affects CENP-C stability at centromeres and causes chromosome segregation errors in young oocytes, a phenotype not observed in mitosis. The expression of exogenous CENP-C rescues these defects via CENP-B-dependent centromere binding, supporting a link between centromere weakening and meiotic errors. This intervention also partially improves chromosome alignment in oocytes from older animals. Together, these findings implicate centromere weakening, alongside cytoskeletal disorganization, in the age-related decline in chromosome segregation fidelity in oocytes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220130","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

ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes.

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-20 DOI: 10.1083/jcb.202511137

Devin Clegg, Amanda Bentley-DeSousa, Agnes Roczniak-Ferguson, Shawn M Ferguson

{"title":"ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes.","authors":"Devin Clegg, Amanda Bentley-DeSousa, Agnes Roczniak-Ferguson, Shawn M Ferguson","doi":"10.1083/jcb.202511137","DOIUrl":"https://doi.org/10.1083/jcb.202511137","url":null,"abstract":"Increased activity of leucine-rich repeat kinase 2 (LRRK2) confers Parkinson's disease risk. LRRK2 dynamically localizes to lysosomal membranes in response to various stresses, yet the mechanisms by which distinct lysosomal perturbations are communicated to LRRK2 remain unclear. Here, we show that inhibition of the lysosomal lipid kinase PIKfyve promotes LRRK2 recruitment and signaling through a pathway that requires the lysosomal chloride/proton antiporter ClC-7. ClC-7 in turn controls the accumulation of multiple Rab GTPases on lysosomes. LRRK2 signaling under these conditions requires its established Rab-binding surfaces, with Rab12 contributing significantly to this response. This pathway operates independently of CASM. In contrast, lysosomal stresses that induce CASM require both Rab-binding sites on LRRK2 and GABARAP for robust LRRK2 signaling. These findings identify ClC-7-dependent lysosomal remodeling and Rab accumulation as key features linking PIKfyve inhibition to LRRK2 signaling and reveal that distinct lysosomal stresses engage different combinations of Rab and GABARAP inputs to activate LRRK2.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227952","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 AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-20 DOI: 10.1083/jcb.202505056

David Vaquero-Pelaz, José-Antonio Rodriguez-Rodriguez, Malina Carmina Ilinca, Esther Casas-Fernández, Amparo Picard, Francisco Del Caño-Ochoa, Isabel Vernia, Toni Gabaldón, Maria Angeles Juanes, Ethel Queralt

{"title":"The AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.","authors":"David Vaquero-Pelaz, José-Antonio Rodriguez-Rodriguez, Malina Carmina Ilinca, Esther Casas-Fernández, Amparo Picard, Francisco Del Caño-Ochoa, Isabel Vernia, Toni Gabaldón, Maria Angeles Juanes, Ethel Queralt","doi":"10.1083/jcb.202505056","DOIUrl":"https://doi.org/10.1083/jcb.202505056","url":null,"abstract":"Accurate chromosome segregation during mitosis requires the precise regulation of separase, a protease that cleaves cohesin to trigger the separation of sister chromatids. Here, we identify the AMPK-activating kinase Sak1 as a novel regulator of separase in Saccharomyces cerevisiae. Using a suppressor screen, we discovered a hypermorphic SAK1-E50K allele that restored separase activity and nuclear localization in esp1-2 and pds1Δ mutants. We demonstrated that Sak1 phosphorylates separase independently of Snf1 activation, enhancing its enzymatic function and promoting nuclear accumulation. Loss of Sak1 delays Cdc14 activation and phenocopies FEAR pathway defects, establishing Sak1 as a mitotic regulator. Extending these findings to humans, we demonstrated that human separase and the tumor suppressor kinase LKB1, which is homologous to Sak1, physically associate. This finding reveals an evolutionarily conserved regulatory link between LKB1 and separase, highlighting the kinase-protease interplay as a critical mechanism for ensuring faithful mitotic progression.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227988","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

MOSPD3 mediates the ER recruitment of ATG2A to promote autophagy. MOSPD3介导ATG2A的内质网募集，促进自噬。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-07 DOI: 10.1083/jcb.202601047

Yuanjiao Du, Tiantian Zhou, Yazhou Liu, Nanxin Ye, Bing Zou, Weiping Chang, Lin Deng, Wei-Ke Ji

引用次数: 0

Different variants, different cellular outcomes: Balanced KIF1A activity shapes synapse development. 不同的变异，不同的细胞结果：平衡的KIF1A活性决定突触的发育。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-10-13 DOI: 10.1083/jcb.202608141

Shinsuke Niwa

引用次数: 0