Journal of Cell Biology最新文献

Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-09 DOI: 10.1083/jcb.202403154

Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman

{"title":"Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.","authors":"Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman","doi":"10.1083/jcb.202403154","DOIUrl":"10.1083/jcb.202403154","url":null,"abstract":"Cell size and biosynthetic capacity generally increase with increased DNA content. Somatic polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood. Here, we show that polyploidy in the Caenorhabditis elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with dilute mRNA. Highly expressed transcripts were more sensitive to this mRNA dilution, whereas lowly expressed genes were partially compensated-in part by loading more RNA Polymerase II on the remaining genomes. Polyploidy-deficient animals produced fewer and slower-growing offspring, consistent with reduced synthesis of highly expressed yolk proteins. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing the expression of translational machinery at the expense of specialized, cell-type-specific proteins.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800922","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

Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-17 DOI: 10.1083/jcb.202405115

Ezekiel C Thomas, Jeffrey K Moore

引用次数: 0

Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-24 DOI: 10.1083/jcb.202403140

Alia R Edington, Olivia M Connor, Abigail C Love, Madeleine Marlar-Pavey, Jonathan R Friedman

{"title":"Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events.","authors":"Alia R Edington, Olivia M Connor, Abigail C Love, Madeleine Marlar-Pavey, Jonathan R Friedman","doi":"10.1083/jcb.202403140","DOIUrl":"https://doi.org/10.1083/jcb.202403140","url":null,"abstract":"While extensive work has examined the mechanisms of mitochondrial fission, it remains unclear whether internal mitochondrial proteins in metazoans play a direct role in the process. Previously, the yeast inner membrane protein Mdm33 was shown to be required for normal mitochondrial morphology and has been hypothesized to be involved in mitochondrial fission. However, it is unknown whether Mdm33 plays a direct role, and it is not thought to have a mammalian homolog. Here, we use a bioinformatic approach to identify a structural ortholog of Mdm33 in humans, CCDC51 (also called MITOK), whose depletion phenocopies loss of Mdm33. We find that knockdown of CCDC51 also leads to reduced rates of mitochondrial fission. Further, we spatially and temporally resolve Mdm33 and CCDC51 to a subset of mitochondrial fission events. Finally, we show that CCDC51 overexpression promotes its spatial association with Drp1 and induces mitochondrial fragmentation, suggesting it is a positive effector of mitochondrial fission. Together, our data reveal that Mdm33 and CCDC51 are functionally conserved and suggest that internal mitochondrial proteins are directly involved in at least a subset of mitochondrial fission events in human cells.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882095","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

Identification of the Polo-like kinase substrate required for homologous synapsis. 鉴定同源突触所需的Polo样激酶底物

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202408092

Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim

{"title":"Identification of the Polo-like kinase substrate required for homologous synapsis.","authors":"Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim","doi":"10.1083/jcb.202408092","DOIUrl":"10.1083/jcb.202408092","url":null,"abstract":"The synaptonemal complex (SC) is a zipper-like protein structure that aligns homologous chromosome pairs and regulates recombination during meiosis. Despite its conserved appearance and function, how synapsis occurs between chromosome axes remains elusive. Here, we demonstrate that Polo-like kinases (PLKs) phosphorylate a single conserved residue in the disordered C-terminal tails of two paralogous SC subunits, SYP-5 and SYP-6, to establish an electrostatic interface between the SC central region and chromosome axes in C. elegans. While SYP-5/6 phosphorylation is dispensable for the ability of SC proteins to self-assemble, local phosphorylation by PLKs at the pairing center is crucial for SC elongation between homologous chromosome axes. Additionally, SYP-5/6 phosphorylation is essential for asymmetric SC disassembly and proper PLK-2 localization after crossover designation, which drives chromosome remodeling required for homolog separation during meiosis I. This work identifies a key regulatory mechanism by which localized PLK activity mediates the SC-axis interaction through phosphorylation of SYP-5/6, coupling synapsis initiation to homolog pairing.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828628","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

An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-10 DOI: 10.1083/jcb.202404003

Duligengaowa Wuergezhen, Eleonore Gindroz, Ritsuko Morita, Kei Hashimoto, Takaya Abe, Hiroshi Kiyonari, Hironobu Fujiwara

{"title":"An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.","authors":"Duligengaowa Wuergezhen, Eleonore Gindroz, Ritsuko Morita, Kei Hashimoto, Takaya Abe, Hiroshi Kiyonari, Hironobu Fujiwara","doi":"10.1083/jcb.202404003","DOIUrl":"10.1083/jcb.202404003","url":null,"abstract":"Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors. Epithelial progenitors are displaced with directionally expanding BMs but do not actively migrate on stationary BM. The addition of a matrix metalloproteinase inhibitor delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Our findings highlight the spatially distinct dynamics of BM and their key roles in orchestrating progenitor cell behavior and organ shape during development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800912","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 proteome-wide yeast degron collection for the dynamic study of protein function.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-18 DOI: 10.1083/jcb.202409050

Rosario Valenti, Yotam David, Dunya Edilbi, Benjamin Dubreuil, Angela Boshnakovska, Yeynit Asraf, Tomer-Meir Salame, Ehud Sass, Peter Rehling, Maya Schuldiner

{"title":"A proteome-wide yeast degron collection for the dynamic study of protein function.","authors":"Rosario Valenti, Yotam David, Dunya Edilbi, Benjamin Dubreuil, Angela Boshnakovska, Yeynit Asraf, Tomer-Meir Salame, Ehud Sass, Peter Rehling, Maya Schuldiner","doi":"10.1083/jcb.202409050","DOIUrl":"https://doi.org/10.1083/jcb.202409050","url":null,"abstract":"Genome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies \"on demand\" protein depletion to overcome these limitations. Here, each protein is tagged with a green fluorescent protein (GFP) and an auxin-inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846662","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

Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-02 DOI: 10.1083/jcb.202406107

Claudia Morais Parada, Ching-Cher Sanders Yan, Cheng-Yu Hung, I-Ping Tu, Chao-Ping Hsu, Yu-Ling Shih

{"title":"Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli.","authors":"Claudia Morais Parada, Ching-Cher Sanders Yan, Cheng-Yu Hung, I-Ping Tu, Chao-Ping Hsu, Yu-Ling Shih","doi":"10.1083/jcb.202406107","DOIUrl":"10.1083/jcb.202406107","url":null,"abstract":"Cell division in Escherichia coli is intricately regulated by the MinD and MinE proteins, which form oscillatory waves between cell poles. These waves manifest as concentration gradients that reduce MinC inhibition at the cell center, thereby influencing division site placement. This study explores the plasticity of the MinD gradients resulting from the interdependent interplay between molecular interactions and diffusion in the system. Through live cell imaging, we observed that as cells elongate, the gradient steepens, the midcell concentration decreases, and the oscillation period stabilizes. A one-dimensional model investigates kinetic rate constants representing various molecular interactions, effectively recapitulating our experimental findings. The model reveals the nonlinear dynamics of the system and a dynamic equilibrium among these constants, which underlie variable concentration gradients in growing cells. This study enhances quantitative understanding of MinD oscillations within the cellular environment. Furthermore, it emphasizes the fundamental role of concentration gradients in cellular processes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769243","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

Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-05 DOI: 10.1083/jcb.202405170

Kai He, Xiaobo Sun, Chuan Chen, San Luc, Jielu Hao Robichaud, Yingyi Zhang, Yan Huang, Biyun Ji, Pei-I Ku, Radhika Subramanian, Kun Ling, Jinghua Hu

{"title":"Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation.","authors":"Kai He, Xiaobo Sun, Chuan Chen, San Luc, Jielu Hao Robichaud, Yingyi Zhang, Yan Huang, Biyun Ji, Pei-I Ku, Radhika Subramanian, Kun Ling, Jinghua Hu","doi":"10.1083/jcb.202405170","DOIUrl":"10.1083/jcb.202405170","url":null,"abstract":"Tubulin polyglutamylation is a posttranslational modification that occurs primarily along the axoneme of cilia. Defective axoneme polyglutamylation impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, the precise mechanisms regulating proper axoneme polyglutamylation remain vague. Here, we show that cyclin-dependent kinase 6 (CDK6), but not its paralog CDK4, localizes to the cilia base and suppresses axoneme polyglutamylation by phosphorylating RAB11 family interacting protein 5 (FIP5) at site S641, a critical regulator of cilia import of glutamylases. S641 phosphorylation disrupts the ciliary recruitment of FIP5 and its association with RAB11, thereby reducing the ciliary import of glutamylases. Encouragingly, the FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore cilia function in JBTS cells with defective glutamylation. In summary, our study elucidates the regulatory mechanisms governing axoneme polyglutamylation and suggests that developing CDK6-specific inhibitors could be a promising therapeutic strategy to enhance cilia function in ciliopathy patients.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785848","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

Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-12-24 DOI: 10.1083/jcb.202409104

Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman

{"title":"Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.","authors":"Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman","doi":"10.1083/jcb.202409104","DOIUrl":"https://doi.org/10.1083/jcb.202409104","url":null,"abstract":"Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's disease (PD), occurring before widespread protein aggregation, neuronal loss, and cognitive decline. While the field has focused on the aggregation of Tau and α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even before their aggregation. Therefore, understanding the mechanisms by which Tau and α-Syn affect presynaptic terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses and potentially halting neurodegeneration. This review focuses on the molecular defects that converge on presynaptic dysfunction caused by Tau and α-Syn. Both proteins have physiological roles in synapses. However, during disease, they acquire abnormal functions due to aberrant interactions and mislocalization. We provide an overview of current research on different essential presynaptic pathways influenced by Tau and α-Syn. Finally, we highlight promising therapeutic targets aimed at maintaining synaptic function in both tauopathies and synucleinopathies.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882093","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

Structural response of microtubule and actin cytoskeletons to direct intracellular load. 微管和肌动蛋白细胞骨架对细胞内直接负荷的结构反应。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-02-03 Epub Date: 2024-11-15 DOI: 10.1083/jcb.202403136

Ryota Orii, Hirokazu Tanimoto

{"title":"Structural response of microtubule and actin cytoskeletons to direct intracellular load.","authors":"Ryota Orii, Hirokazu Tanimoto","doi":"10.1083/jcb.202403136","DOIUrl":"10.1083/jcb.202403136","url":null,"abstract":"Microtubule and actin are the two major cytoskeletal polymers that form organized functional structures in the interior of eukaryotic cells. Although the structural mechanics of the cytoskeleton has been extensively studied by direct manipulations in in vitro reconstitution systems, such unambiguous characterizations inside the living cell are sparse. Here, we report a comprehensive analysis of how the microtubule and actin cytoskeletons structurally respond to direct intracellular load. Ferrofluid-based intracellular magnetic tweezers reveal rheological properties of the microtubule complex primarily determined by filamentous actin. The strain fields of the microtubule complex and actin meshwork follow the same scaling, suggesting that the two cytoskeletal systems behave as an integrated elastic body. The structural responses of single microtubules to contact and remote forces further evidence that the individual microtubules are enclosed by the elastic medium of actin. These results, directly characterizing the microtubule and actin cytoskeletons as an interacting continuum throughout the cytoplasm, serve as a cornerstone for the physical understanding of intracellular organization.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638716","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